Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Cysteamine: A mercaptoethylamine compound that is endogenously derived from the COENZYME A degradative pathway. The fact that cysteamine is readily transported into LYSOSOMES where it reacts with CYSTINE to form cysteine-cysteamine disulfide and CYSTEINE has led to its use in CYSTINE DEPLETING AGENTS for the treatment of CYSTINOSIS.Peptide Nucleic Acids: DNA analogs containing neutral amide backbone linkages composed of aminoethyl glycine units instead of the usual phosphodiester linkage of deoxyribose groups. Peptide nucleic acids have high biological stability and higher affinity for complementary DNA or RNA sequences than analogous DNA oligomers.Wasp Venoms: Venoms produced by the wasp (Vespid) family of stinging insects, including hornets; the venoms contain enzymes, biogenic amines, histamine releasing factors, kinins, toxic polypeptides, etc., and are similar to bee venoms.Galanin: A neuropeptide of 29-30 amino acids depending on the species. Galanin is widely distributed throughout the BRAIN; SPINAL CORD; and INTESTINES. There are various subtypes of GALANIN RECEPTORS implicating roles of galanin in regulating FOOD INTAKE; pain perception; memory; and other neuroendocrine functions.Drug Delivery Systems: Systems for the delivery of drugs to target sites of pharmacological actions. Technologies employed include those concerning drug preparation, route of administration, site targeting, metabolism, and toxicity.Cell Membrane Permeability: A quality of cell membranes which permits the passage of solvents and solutes into and out of cells.Drug Carriers: Forms to which substances are incorporated to improve the delivery and the effectiveness of drugs. Drug carriers are used in drug-delivery systems such as the controlled-release technology to prolong in vivo drug actions, decrease drug metabolism, and reduce drug toxicity. Carriers are also used in designs to increase the effectiveness of drug delivery to the target sites of pharmacological actions. Liposomes, albumin microspheres, soluble synthetic polymers, DNA complexes, protein-drug conjugates, and carrier erythrocytes among others have been employed as biodegradable drug carriers.Gene Products, tat: Trans-acting transcription factors produced by retroviruses such as HIV. They are nuclear proteins whose expression is required for viral replication. The tat protein stimulates LONG TERMINAL REPEAT-driven RNA synthesis for both viral regulatory and viral structural proteins. tat stands for trans-activation of transcription.Liposomes: Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Lipid Bilayers: Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes.Peptide Library: A collection of cloned peptides, or chemically synthesized peptides, frequently consisting of all possible combinations of amino acids making up an n-amino acid peptide.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Antimicrobial Cationic Peptides: Small cationic peptides that are an important component, in most species, of early innate and induced defenses against invading microbes. In animals they are found on mucosal surfaces, within phagocytic granules, and on the surface of the body. They are also found in insects and plants. Among others, this group includes the DEFENSINS, protegrins, tachyplesins, and thionins. They displace DIVALENT CATIONS from phosphate groups of MEMBRANE LIPIDS leading to disruption of the membrane.Peptides, Cyclic: Peptides whose amino and carboxy ends are linked together with a peptide bond forming a circular chain. Some of them are ANTI-INFECTIVE AGENTS. Some of them are biosynthesized non-ribosomally (PEPTIDE BIOSYNTHESIS, NON-RIBOSOMAL).Libraries, Digital: Libraries in which a major proportion of the resources are available in machine-readable format, rather than on paper or MICROFORM.Smad3 Protein: A receptor-regulated smad protein that undergoes PHOSPHORYLATION by ACTIVIN RECEPTORS, TYPE I. Activated Smad3 can bind directly to DNA, and it regulates TRANSFORMING GROWTH FACTOR BETA and ACTIVIN signaling.tat Gene Products, Human Immunodeficiency Virus: Proteins encoded by the TAT GENES of the HUMAN IMMUNODEFICIENCY VIRUS.Smad4 Protein: A signal transducing adaptor protein and tumor suppressor protein. It forms a complex with activated RECEPTOR-REGULATED SMAD PROTEINS. The complex then translocates to the CELL NUCLEUS and regulates GENETIC TRANSCRIPTION of target GENES.Smad Proteins: A family of proteins that are involved in the translocation of signals from TGF-BETA RECEPTORS; BONE MORPHOGENETIC PROTEIN RECEPTORS; and other surface receptors to the CELL NUCLEUS. They were originally identified as a class of proteins that are related to the mothers against decapentaplegic protein, Drosophila and sma proteins from CAENORHABDITIS ELEGANS.Smad1 Protein: A receptor-regulated smad protein that undergoes PHOSPHORYLATION by BONE MORPHOGENETIC PROTEIN RECEPTORS. It regulates BONE MORPHOGENETIC PROTEIN signaling and plays an essential role in EMBRYONIC DEVELOPMENT.Nanoparticles: Nanometer-sized particles that are nanoscale in three dimensions. They include nanocrystaline materials; NANOCAPSULES; METAL NANOPARTICLES; DENDRIMERS, and QUANTUM DOTS. The uses of nanoparticles include DRUG DELIVERY SYSTEMS and cancer targeting and imaging.Quantum Dots: Nanometer sized fragments of semiconductor crystalline material which emit PHOTONS. The wavelength is based on the quantum confinement size of the dot. They can be embedded in MICROBEADS for high throughput ANALYTICAL CHEMISTRY TECHNIQUES.Fluorescent Dyes: Agents that emit light after excitation by light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags.Genetic Therapy: Techniques and strategies which include the use of coding sequences and other conventional or radical means to transform or modify cells for the purpose of treating or reversing disease conditions.Genetic Vectors: DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.Gene Transfer Techniques: The introduction of functional (usually cloned) GENES into cells. A variety of techniques and naturally occurring processes are used for the gene transfer such as cell hybridization, LIPOSOMES or microcell-mediated gene transfer, ELECTROPORATION, chromosome-mediated gene transfer, TRANSFECTION, and GENETIC TRANSDUCTION. Gene transfer may result in genetically transformed cells and individual organisms.RNA-Induced Silencing Complex: A multicomponent, ribonucleoprotein complex comprised of one of the family of ARGONAUTE PROTEINS and the "guide strand" of the one of the 20- to 30-nucleotide small RNAs. RISC cleaves specific RNAs, which are targeted for degradation by homology to these small RNAs. Functions in regulating gene expression are determined by the specific argonaute protein and small RNA including siRNA (RNA, SMALL INTERFERING), miRNA (MICRORNA), or piRNA (PIWI-INTERACTING RNA).RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Dendrimers: Tree-like, highly branched, polymeric compounds. They grow three-dimensionally by the addition of shells of branched molecules to a central core. The overall globular shape and presence of cavities gives potential as drug carriers and CONTRAST AGENTS.Hemolytic Agents: Substances that are toxic to blood in general, including the clotting mechanism; hematotoxins may refer to the hematopoietic system.Mitochondria: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)Organophosphorus Compounds: Organic compounds that contain phosphorus as an integral part of the molecule. Included under this heading is broad array of synthetic compounds that are used as PESTICIDES and DRUGS.Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.Scattering, Small Angle: Scattering of a beam of electromagnetic or acoustic RADIATION, or particles, at small angles by particles or cavities whose dimensions are many times as large as the wavelength of the radiation or the de Broglie wavelength of the scattered particles. Also know as low angle scattering. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed) Small angle scattering (SAS) techniques, small angle neutron (SANS), X-ray (SAXS), and light (SALS, or just LS) scattering, are used to characterize objects on a nanoscale.Arginine: An essential amino acid that is physiologically active in the L-form.Osmolar Concentration: The concentration of osmotically active particles in solution expressed in terms of osmoles of solute per liter of solution. Osmolality is expressed in terms of osmoles of solute per kilogram of solvent.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Adhesives: Substances that cause the adherence of two surfaces. They include glues (properly collagen-derived adhesives), mucilages, sticky pastes, gums, resins, or latex.Molecular Dynamics Simulation: A computer simulation developed to study the motion of molecules over a period of time.HandbooksManuals as Topic: Books designed to give factual information or instructions.Cartoons as Topic: Images used to comment on such things as contemporary events, social habits, or political trends; usually executed in a broad or abbreviated manner.Trifluoroethanol: A non-aqueous co-solvent that serves as tool to study protein folding. It is also used in various pharmaceutical, chemical and engineering applications.

Passage of cell-penetrating peptides across a human epithelial cell layer in vitro. (1/188)

Cell barriers are essential for the maintenance and regulation of the microenvironments of the human body. Cell-penetrating peptides have simplified the delivery of bioactive cargoes across the plasma membrane. Here, the passage of three cell-penetrating peptides (transportan, the transportan analogue transportan 10, and penetratin) across a Caco-2 human colon cancer cell layer in vitro was investigated. The peptides were internalized into epithelial Caco-2 cells as visualized by indirect fluorescence microscopy and quantified by fluorimetry. Studies of peptide outflow from cells showed that the peptides were in equilibrium across the plasma membrane. The ability of the peptides to cross a Caco-2 cell layer was tested in a two-chambered model system. After 120 min, 7.0%, 2.8% and 0.6% of added transportan, transportan 10 and penetratin respectively was detected in the lower chamber. Both transportan and transportan 10 reversibly decreased the trans-epithelial electrical resistance of the barrier model, with minimum values after 60 min of 46% and 60% of control respectively. Penetratin did not affect the resistance of the cell layer to the same extent. Although transportan markedly increased the passage of ions, the paracellular flux of 4.4 kDa fluorescein-labelled dextran was limited. In conclusion, the results indicate that the transportan peptides pass the epithelial cell layer mainly by a mechanism involving a transcellular pathway.  (+info)

TAT peptide and its conjugates: proteolytic stability. (2/188)

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MALDI-TOF mass spectrometry: a powerful tool to study the internalization of cell-penetrating peptides. (3/188)

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Lipid domain separation, bilayer thickening and pearling induced by the cell penetrating peptide penetratin. (4/188)

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Cell-penetrating peptide exploited syndecans. (5/188)

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Cell biology meets biophysics to unveil the different mechanisms of penetratin internalization in cells. (6/188)

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Peptide-mediated protein delivery-which pathways are penetrable? (7/188)

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Morpholinos and their peptide conjugates: therapeutic promise and challenge for Duchenne muscular dystrophy. (8/188)

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*Cell-penetrating peptide

Langel (Ed.), Cell-penetrating peptides, 2007, pp. 387-408. S. El-Andaloussi, T. Holm, Ü. Langel, Cell-penetrating peptides: ... Instant insight into cell penetrating peptides from the Royal Society of Chemistry www.cell-penetrating-peptides.com Fully ... Handbook of Cell-Penetrating Peptides, Second Edition, 2007 Stetsenko, D.A. and Gait, M.J., Efficient conjugation of peptides ... Cell-penetrating peptides (CPPs) are short peptides that facilitate cellular intake/uptake of various molecular equipment (from ...

*Transcriptome in vivo analysis tag

Cell-penetrating peptide CPP: guides the TIVA tag through cell membranes into tissues. It is linked to the TIVA tag by a ... Madani F, Lindberg S, Langel U, Futaki S, Gräslund A (2011). "Mechanisms of cellular uptake of cell-penetrating peptides". J ... TIVA tags are created initially via solid-phase synthesis with the cell-penetrating peptide conjugated afterwards. The ... the cell is imaged with the confocal microscope. Using a glass pipette, the photolysed cell is isolated by aspiration. Cells ...

*Hadrucalcin

... appears to be an even more potent cell penetrating peptide. A Hadrucalcin derivative has been used as a carrier for ... Cell-Penetrating Nanobiosensors for Pointillistic Intracellular Ca 2+ - Transient Detection. 2014.. ... Hadrucalcin is a peptide toxin from the scorpion calcine family. The mature Hadrucalcin peptide is composed of 35 amino acids, ... Cell penetration properties of a highly efficient mini maurocalcine Peptide. Pharmaceuticals (Basel). 2013;6(3):320-39. doi: ...

*Kim Janda

"A cell-penetrating peptide from a novel pVII-pIX phage-displayed random peptide library". Bioorganic & Medicinal Chemistry. 10 ... Further mechanistic studies of this peptide uncovered a dimerization "switch" that modulates the cell-penetrating activity. In ... By panning this library against a B lymphoctye cell line, a unique cell-binding and internalizing peptide was discovered. ... in the Internalization Mechanism of a Cell-Penetrating Peptide". Journal of the American Chemical Society. 127 (2): 538-539. ...

*Morpholino

"Stability of cell-penetrating peptide-Morpholino oligomer conjugates in human serum and in cells". Bioconjug Chem. 18 (1): 50- ... cells in adult organisms can be accomplished by using covalent conjugates of Morpholino oligos with cell-penetrating peptides, ... Stability and Toxicity of a Cell-Penetrating Peptide-Morpholino Oligomer Conjugate". Bioconjug Chem. 18 (4): 1325-31. doi: ... The Minor Spliceosome Acts outside the Nucleus and Controls Cell Proliferation". Cell. 131 (4): 718-29. doi:10.1016/j.cell. ...

*Tat (HIV)

Tat contains a protein transduction domain, which is therefore known as a cell-penetrating peptide. Originally characterised by ... It can be absorbed by cells that are not infected with HIV, and can act directly as a toxin producing cell death via apoptosis ... Schwarze SR, Hruska KA, Dowdy SF (July 2000). "Protein transduction: unrestricted delivery into all cells?". Trends Cell Biol. ... this domain allows Tat to enter cells by crossing the cell membrane. The amino acid sequence of the protein transduction domain ...

*Gajendra Pal Singh Raghava

Scientific Reports 3: 1607 CellPPD: In silico approaches for designing highly effective cell penetrating peptides. Journal of ... PLoS ONE 8(6): e67008 Lbtope: Improved Method for Linear B-Cell Epitope Prediction Using Antigen's Primary Sequence. PLoS ONE 8 ... In Silico Approach for Predicting Toxicity of Peptides and Proteins. [1] "Notable bioinformatician - Dr Gajendra Pal Singh ... Computational approach for designing tumor homing peptides. ...

*West Nile fever

Morpholino antisense oligos conjugated to cell penetrating peptides have been shown to partially protect mice from WNV disease ... Pleocytosis, an increase of white blood cells in cerebrospinal fluid, is also present. Changes in consciousness are not usually ... Disconnect of upper motor neuron influences on the anterior horn cells possibly by myelitis or glutamate excitotoxicity have ...

*Pepducin

... s are cell-penetrating peptides that act as intracellular modulators of signal transference from receptors to G ... "Activation and inhibition of G protein-coupled receptors by cell-penetrating membrane-tethered peptides". Proc. Natl. Acad. Sci ... "Suppression of Arterial Thrombosis with Affecting Hemostatic Parameters with a Cell-Penetrating PAR1 Pepducin". Circulation. ... A pepducin molecule consists of a short peptide derived from a GPCR intracellular loop tethered to a hydrophobic moiety. This ...

*Erkki Ruoslahti

... sulfate proteoglycans cooperate in cellular uptake of nanoparticles functionalized by cationic cell-penetrating peptides". Sci ... The prototype tumor-penetrating peptide, iRGD, is about to enter clinical trials as an enhancer of cancer therapies. This ... These tumor-penetrating peptides selectively home to tumor vessels, where they activate a transport pathway that delivers the ... Teesalu, T.; Sugahara, K. N.; Kotamraju, V. R.; Ruoslahti, E. (2009). "C-end rule peptides mediate neuropilin-1-dependent cell ...

*Igor V. Komarov

"Delivery of SiC-based nanoparticles into live cells driven by cell-penetrating peptides SAP and SAP-E". RSC Advances. 5 (26). ... In the area of nanotechnology, Igor V. Komarov's research group studied cell-penetrating peptides as carriers for carbon-based ... with a purpose of using them as labels to study peptides in lipid bilayers by solid-state NMR spectroscopy. Igor V. Komarov's ... photocontrollable peptides - potential candidates for photopharmacology drugs. Photopharmacology drugs can be administered in ...

*Gold nanoparticles in chemotherapy

"Cell-Penetrating Peptide-Modified Gold Nanoparticles for the Delivery of Doxorubicin to Brain Metastatic Breast Cancer". ... They concluded a 15% cell viability and dose dependent cell damage. Reduction in cell viability was detected in vivo ... Studies in human leukemia cells revealed that prolonged exposure in AuNPs did not harm the cells, even at ~100 μM of Au. Rather ... A tumor consists of a multitude of cell types, and thus targeting a single type of cell is ineffective and potentially ...

*Aldoxorubicin

Walker, L; Perkins, E; Kratz, F; Raucher, D (Oct 2012). "Cell penetrating peptides fused to a thermally targeted biopolymer ... for metastatic small cell lung cancer Treatment of advanced or metastatic pancreatic ductal adenocarcinoma Comparison of ...

*Nanoparticles for drug delivery to the brain

... because their positive charges assist binding on the brain's endothelial cells. Using TAT-peptides, a cell-penetrating peptide ... By transfection of endothelial cells through the use of lipoplexes, physical alterations in the cells could be made. These ... Oils rich in omega-3 fatty acids especially contain important factors that aid in penetrating the tight junctions of the BBB. ... The drug used was hexapeptide dalargin, an anti-nociceptive peptide that cannot cross the BBB alone. It was encapsulated in ...

*Penicillium digitatum

... vapour heat and cell-penetrating anti-fungal peptides. Penicillium digitatum can be identified in the laboratory using a ... "Understanding the mechanism of action of cell-penetrating antifungal peptides using the rationally designed hexapeptide PAF26 ... The hyphal cells are haploid, although individual hyphal compartments may contain many genetically identical nuclei. During the ... Revealing diverse modes of action and biological roles of antifungal peptides. 26 (4): 146-155. doi:10.1016/j.fbr.2012.10.003. ...

*Peptide nucleic acid

Though an unmodified PNA cannot readily cross cell membranes to enter the cytosol, covalently coupling a cell penetrating ... Peptide synthesis Oligonucleotide synthesis Glycol nucleic acid Threose nucleic acid Clicked peptide polymer Nielsen PE, Egholm ... Peptide nucleic acid (PNA) is an artificially synthesized polymer similar to DNA or RNA. It was invented by Peter E. Nielsen ( ... June 2006). "Peptide Nucleic Acid (PNA): A Review". Journal of Chemical Technology and Biotechnology. An overview of the PNA ...

*CPP

... a type of propeller Cell-penetrating peptide, are short polycationic sequences Central precocious puberty, a condition in which ...

*Transporter Classification Database

Family 2.B.9 The Cell Penetrating Peptide (CPP) Functional Family 2.B.10 The Synthetic CPP, Transportan Family 2.B.11 The ... Fusion Peptide (HIV-FP) Family 1.G.17 The Bovine Leukemia Virus Envelop Glycoprotein (BLV-Env) Family 1.G.18 The SARS-CoV ... β-sheet Peptide Family 1.D.18 The Pore-forming Guanosine-Bile Acid Conjugate Family 1.D.19 Ca2+ Channel-forming Drug, Digitoxin ... Gamma-Cycic Peptide (AGCP) Family 1.D.61 The Anionophoric 2,6-Bis(Benzimidazol-2-yl)Pyridine (ABBP) Family 1.D.62 The Bis- ...

*Electroporation

... though depending on what is being transferred cell-penetrating peptides or CellSqueeze could also be used. Electroporation ... Cell fusion is of interest not only as an essential process in cell biology, but also as a useful method in biotechnology and ... Optimization of bulk cell electrofusion in vitro for production of human-mouse heterohybridoma cells. Bioelectrochemistry 74, ... This allows for a quicker recovery, and facilitates a more rapid replacement of dead tumor cells with healthy cells. Before ...

*Influenza research

Morpholinos conjugated with cell penetrating peptides have been shown effective in protecting mice from influenza A. "Several ... the pandemic H5N1 might be lethal to chickens Cell culture (cell-based) manufacturing technology can be applied to influenza ... In contrast, cell culture manufacturing technology can be applied to influenza vaccines as they are with most viral vaccines (e ... Novartis' other cell-based vaccine production facility is in Marburg, Germany." According to the United States Department of ...

*Silver nanoparticle

... which acts as a cell penetrating peptide (CPP). Generally, AgNP effectiveness is limited due to the lack of efficient cellular ... As the silver nano particles come in contact with the bacteria, they adhere to the cell wall and cell membrane. Once bound, ... Although it varies for every type of cell proposed, as their cell membrane composition varies greatly, It has been seen that in ... Fodale, V.; Pierobon, M.; Liotta, L.; Petricoin, E. (2011). "Mechanism of cell adaptation: when and how do cancer cells develop ...

*Spotlight Innovation

... entered into a research agreement with Atlanta-based Emory University to study the viability of the cell-penetrating peptide ... that could cause cell death in malignant cancer cells. Crotoxin was tested on patients in the George Pompidou University ...

*Vectors in gene therapy

Cell-penetrating peptides (CPPs), also known as peptide transduction domains (PTDs), are short peptides (< 40 amino acids) that ... "Do cell-penetrating peptides actually "penetrate" cellular membranes?". Molecular Therapy. 20 (4): 695-697. doi:10.1038/mt. ... scope and limitations by the application of cell-penetrating peptides". Journal of Peptide Science. 20 (10): 760-784. doi: ... 2014). "Cell-penetrating peptides: Design, synthesis, and applications". ACS Nano. 8 (3): 1972-1994. doi:10.1021/nn4057269. ...

*Anabolic steroid

Water-soluble peptide hormones cannot penetrate the fatty cell membrane and only indirectly affect the nucleus of target cells ... The pharmacodynamic action of AAS begin when the exogenous hormone penetrates the membrane of the target cell and binds to an ... AAS also affect the number of cells that develop into fat-storage cells, by favouring cellular differentiation into muscle ... which increases the production of red blood cells. Through a number of mechanisms AAS stimulate the formation of muscle cells ...

*Anne Ulrich

The main systems of interest are: Mechanisms of membrane-active peptides with antimicrobial, cell-penetrating, fusogenic, or ... and protein translocation systems Self-assembly of amyloidogenic peptides and "charge-zipper" proteins in membranes Ulrich ...

*Nephron

Podocytes, Endothelial cells, and Glomerular mesangial cell are present. Nephrology Urology Pocock, Gillian; Richards, ... atrial natriuretic peptide (sodium) and brain natriuretic peptide (sodium). A countercurrent system in the renal medulla ... Cortical nephrons (the majority of nephrons) start high in the cortex and have a short loop of Henle which does not penetrate ... It contains three components: the macula densa, juxtaglomerular cells, and extraglomerular mesangial cells.[citation needed] ...
Identification of a novel cell-penetrating peptide targeting human glioblastoma cell lines as a cancer-homing transporterIdentification of a novel cell-penetrating peptide targeting human glioblastoma cell lines as a cancer-homing transporterAA11542044 ...
The ability of cell-penetrating peptides to cross plasma membranes has been explored for various applications, including the delivery of bioactive molecules to inhibit disease-causing cellular processes. The uptake mechanisms by which cell-penetrating peptides enter cells depend on the conditions, such as the cell line the concentration and the temperature. To be used as therapeutics, each novel cell-penetrating peptide needs to be fully characterized, including their physicochemical properties, their biological activity and their uptake mechanism. Our group has developed a series of highly performing, non-toxic cell-penetrating peptides, all derived from the original sequence of transportan 10. These analogs are called PepFects and NickFects and they are now a diverse family of N-terminally stearylated peptides. These peptides are known to form noncovalent, nano-sized complexes with diverse oligonucleotide cargoes. One bottleneck that limits the use of this technology for gene therapy ...
Cell-penetrating peptides (CPPs) are prominent delivery vehicles to confer cellular entry of (bio-) macromolecules. Internalization efficiency and uptake mechanism depend, next to the type of CPP and cargo, also on cell type. Direct penetration of the plasma membrane is the preferred route of entry as this circumvents endolysosomal sequestration. However, the molecular parameters underlying this import mechanism are still poorly defined. Here, we make use of the frequently used HeLa and HEK cell lines to address the role of lipid composition and membrane potential. In HeLa cells, at low concentrations, the CPP nona-arginine (R9) enters cells by endocytosis. Direct membrane penetration occurs only at high peptide concentrations through a mechanism involving activation of sphingomyelinase which converts sphingomyelin into ceramide. In HEK cells, by comparison, R9 enters the cytoplasm through direct membrane permeation already at low concentrations. This direct permeation is strongly reduced at ...
article{d17966db-786f-4d12-a5f5-3a25a837ce80, abstract = {,p,Small-angle X-ray scattering (SAXS) measurements reveal a striking difference in intermolecular interactions between two short highly charged peptides - deca-arginine (R10) and deca-lysine (K10). Comparison of SAXS curves at high and low salt concentration shows that R10 self-associates, while interactions between K10 chains are purely repulsive. The self-association of R10 is stronger at lower ionic strengths, indicating that the attraction between R10 molecules has an important electrostatic component. SAXS data are complemented by NMR measurements and potentials of mean force between the peptides, calculated by means of umbrella-sampling molecular dynamics (MD) simulations. All-atom MD simulations elucidate the origin of the R10- R10 attraction by providing structural information on the dimeric state. The last two C-terminal residues of R10 constitute an adhesive patch formed by stacking of the side chains of two arginine residues ...
Quantitative fluorescence spectroscopy and flow cytometry analyses of cell-penetrating peptides internalization pathways: optimization, pitfalls, comparison with mass spectrometry quantification, Scientific Reports 6, 36938 (2016). Since their discovery twenty years ago, cell-penetrating peptides (CPPs) or protein transduction domains (PTDs) have been described as promising drug delivery systems. There are increasing numbers of successful applications of CPPs/PTDs in vivo. However, one of the limitations to their wide and diverse application is the diversity of their uptake pathways. The CPP and its cargo may end up free in the cytosol and reach their biological target only following translocation, but remain confined in intracellular vesicles after endocytosis, unless subsequent events such as endosomal rupture occur. Along with the development of CPPs/PTDs as vectors to carry various macromolecules for targeted cellular therapies, engineering new CPPs/PTDs with optimized transport and ...
Arginine-rich cell-penetrating peptides (CPP) are widely employed as delivery vehicles for a large variety of macromolecular cargos. As a mechanism-of-action for induction of uptake cross-linking of heparan sulfates and interaction with lipid head groups have been proposed. Here, we employed a multivalent display of the CPP nona-arginine (R9) on a linear dextran scaffold to assess the impact of heparan sulfate and lipid interactions on uptake and membrane perturbation. Increased avidity through multivalency should potentiate molecular phenomena that may only play a minor role if only individual peptides are used. To this point, the impact of multivalency has only been explored for dendrimers, CPP-decorated proteins and nanoparticles. We reasoned that multivalency on a linear scaffold would more faithfully mimic the arrangement of peptides at the membrane at high local peptide concentrations. On average, five R9 were coupled to a linear dextran backbone. The conjugate displayed a direct ...
Genes are the major regulators of biological processes in every living thing. Problems with gene regulation can cause serious problems for the organism; for example, most cancers have some kind of genetic component. Regulation of biological processes using oligonucleotides can potentially be a therapy for any ailment, not just cancer. The problem so far has been that the targets for oligonucleotide-based therapies all reside on the inside of cells, because the cellular plasma membrane is normally impermeable to large and charged molecules (such as oligonucleotides) a delivery method is needed. Cell-penetrating peptides are a class of carrier molecules that are able to induce the cellular membrane into taking them and their cargo molecules into the cells. Understanding how and why cell-penetrating peptides work is one of the first and most important steps towards improving them to the point where they become useful as carriers for oligonucleotide-based therapies. This thesis is comprised of four ...
Regulation of biological processes through the use of genetic elements is a central part of biological research and also holds great promise for future therapeutic applications. Oligonucleotides comprise a class of versatile biomolecules capable of modulating gene regulation. Gene therapy, the concept of introducing genetic elements in order to treat disease, presents a promising therapeutic strategy based on such macromolecular agents. Applications involving charged macromolecules such as nucleic acids require the development of the active pharmaceutical ingredient as well as efficient means of intracellular delivery. Cell-penetrating peptides are a promising class of drug delivery vehicles, capable of translocation across the cell membrane together with molecules otherwise unable to permeate cells, which has gained significant attention. In order to increase the effectiveness of cell-penetrating peptide-mediated delivery, further understanding of the mechanisms of uptake is needed in addition ...
Redesigning linear cell penetrating peptides (CPPs) into a multi-branched topology with short dipeptide branches gave cell penetrating peptide dendrimers (CPPDs) with higher cell penetration, lower toxicity and hemolysis and higher serum stability than linear CPPs. Their use is demonstrated by delivering a c
The use of CPPs (cell-penetrating peptides) as delivery vectors for bioactive molecules has been an emerging field since 1994 when the first CPP, penetratin, was discovered. Since then, several CPPs, including the widely used Tat (transactivator of transcription) peptide, have been developed and utilized to translocate a wide range of compounds across the plasma membrane of cells both in vivo and in vitro. Although the field has emerged as a possible future candidate for drug delivery, little attention has been given to the potential toxic side effects that these peptides might exhibit in cargo delivery. Also, no comprehensive study has been performed to evaluate the relative efficacy of single CPPs to convey different cargos. Therefore we selected three of the major CPPs, penetratin, Tat and transportan 10, and evaluated their ability to deliver commonly used cargos, including fluoresceinyl moiety, double-stranded DNA and proteins (i.e. avidin and streptavidin), and studied their effect on membrane
CPPs (cell-penetrating peptides) facilitate cellular uptake of covalently attached macromolecules, through an as yet controversial mechanism that either involves direct membrane passage or a type of endocytosis. We investigated the potential of the CPPs penetratin and Tat to act as mitochondria-targeting vectors by testing whether they were internalized by isolated mitochondria, and by mitochondria within cells in culture. We also tested peptides conjugated to the mitochondria-targeting moiety triphenylphosphonium. We found no evidence for mitochondrial uptake by penetratin, Tat or their triphenylphosphonium conjugates. This result suggests that CPPs are unsuitable as mitochondria-targeting vectors, and implies an endocytic mode of cellular uptake for CPPs. ...
TY - JOUR. T1 - Better living through peptide-conjugated chemistry. T2 - Next-generation antisense oligonucleotides. AU - McNally, Elizabeth M.. AU - Leverson, Brian D.. PY - 2019/11/1. Y1 - 2019/11/1. N2 - Two different antisense oligonucleotide-based (ASO-based) therapies are currently in clinical use to treat neuromuscular diseases. This success, for Duchenne muscular dystrophy and spinal muscular atrophy, offers hope not only for additional neuromuscular diseases, but also for other disorders that could benefit from RNA-targeted therapies. A major limitation for more widespread application of ASOs relates to relatively poor tissue penetration. In this issue of the JCI, Klein et al. showed that conjugating an ASO with an arginine-rich cell-penetrating peptide, Pip6a, enhanced delivery, resulting in corrective outcome for a mouse model of myotonic dystrophy. Linking ASOs to cell-penetrating peptides, or even other moieties, is an approach currently under development with treatment potential to ...
Cell-penetrating peptides (CPP) have attracted many scientists attention as intracellular delivery tools due to their high cargo molecule transportation efficiency and low cytotoxicity. Therefore, in many research fields CPP, such as HIV-Tat and oligoarginine (Rn), are used to deliver hydrophilic drugs and biomolecules, including proteins, DNA, and RNA. We designed four types of CPP that contained cationic α,α-disubstituted amino acids (Api(C2Gu) and Api(C4Gu)) as helical promoters; i.e., 1-4 [FAM-β-Ala-(l-Arg-l-Arg-Xaa)3-(Gly)3-NH2 (1: Xaa=Api(C2Gu), 2: Xaa=Api(C4Gu)), 3: FAM-β-Ala-(l-Arg)8-Api(C2Gu)-(Gly)3-NH2, and 4: FAM-β-Ala-(l-Arg)5-Api(C2Gu)-(l-Arg)2-Api(C2Gu)-(Gly)3-NH2], and investigated their preferred secondary structures and cell membrane-penetrating ability. As a result, we found that the permeation efficiency of the CPP was affected by the number of helical promoters in their sequences. Specially, peptide 1, which contained three Api(C2Gu) residues, formed a stable helical ...
DUGi: Viewing Item from repository Recercat: This thesis is focused on the development of synthetic approaches to obtain new bioactive peptides. The first part deals with the design of new antimicrobial peptide/cell-penetrating peptide conjugates as anticancer agents. Their conjugation enhanced the activity of the antimicrobial peptides against cancer cells while maintained their low toxicity. These compounds are interesting for the design of new anticancer agents. On the second part, a new versatile methodology for the synthesis of natural fengycin derivatives is described. Our strategy represents the first synthetic approach for the total solid-phase synthesis of these cyclic lipodepsipeptides and can be easily adapted to obtain a wide range of analogues.
DUGi: Viewing Item from repository DUGiDocs: Peptide conjugates incorporating the red-ox active ligands Me2PyTACN or (S,S)-BPBP at the N- or the C-terminus of the cell-penetrating peptide BP16 were synthesized (PyTACN-BP16 (BP341), BP16-PyTACN (BP342), BPBP-BP16 (BP343), and BP16-BPBP (BP344)). Metal binding peptides bearing at the N-terminus the ligand, an additional Lys and a β-Ala were also prepared (PyTACN-βAK-BP16 (BP345) and BPBP-βAK-BP16 (BP346)). Moreover, taking into account the clathrin-dependent endocytic mechanism of BP16, the enzymatic cleavable tetrapeptide Gly-Phe-Leu-Gly was incorporated between the ligand and the N- or C-terminus of BP16 (BPBP-GFLG-BP16 (BP347) and BP16-GLFG-BPBP (BP348). Analysis of the cytotoxicity of all the peptide conjugates showed that: (i) the position of the ligand influenced the IC50 values, (ii) the incorporation of the βAla-Lys dipeptide rendered non active sequences, (iii) peptide conjugates derived from the (S,S)-BPBP ligand were more active than
Author: Jha, D et al.; Genre: Journal Article; Published in Print: 2011-03; Title: CyLoP-1: A Novel Cysteine-Rich Cell-Penetrating Peptide for Cytosolic Delivery of Cargoes
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Transposable elements have emerged as a promising candidate for human non-viral gene-therapy. The Tc1/mariner transposon Sleeping Beauty is to date one of the most efficient transposons in mammals. Sleeping Beauty transposase has so far mostly been delivered to cells via a DNA source. This might cause spontaneous integration of the transposase gene and cause fatal damage to the affected cell. Hence, it would be advantageous to employ a non-genetic source for the transposase. We here show that a novel Cell-penetrating peptide, M918, has the ability to facilitate cellular delivery of both the transposase Sleeping Beauty as a protein and a transposon donor-plasmid carrying an antibiotic resistance gene in vitro. The technique is a simple and straightforward one-step method that might render a safe and efficient delivery platform for Sleeping Beauty mediated gene therapy.. ...
Several recent studies have demonstrated that TAT and other arginine-rich cell penetrating peptides (CPPs) have intrinsic neuroprotective properties in their own right. Examples, we have demonstrated that in addition to TAT, poly-arginine peptides (R8 to R18; containing 8-18 arginine residues) as well as some other arginine-rich peptides are neuroprotective in vitro (in neurons exposed to glutamic acid excitotoxicity and oxygen glucose deprivation) and in the case of R9 in vivo (after permanent middle cerebral artery occlusion in the rat). Based on several lines of evidence, we propose that this neuroprotection is related to the peptides endocytosis-inducing properties, with peptide charge and arginine residues being critical factors. Specifically, we propose that during peptide endocytosis neuronal cell surface structures such as ion channels and transporters are internalised, thereby reducing calcium influx associated with excitotoxicity and other receptor-mediated neurodamaging signalling ...
We investigated the metabolic stability of four cell penetrating peptides (CPPs), namely SAP, hCT(9-32)-br, [Palpha] and [Pbeta], when in contact with either subconfluent HeLa, confluent MDCK or Calu-3 epithelial cell cultures. Additionally, through analysis of their cellular translocation efficiency, we evaluated possible relations between metabolic stability and translocation efficiency. Metabolic degradation kinetics and resulting metabolites were assessed using RP-HPLC and MALDI-TOF mass spectrometry. Translocation efficiencies were determined using fluorescence-activated cell sorting (FACS) and confocal laser scanning microscopy (CLSM). Between HeLa, MDCK and Calu-3 we found the levels of proteolytic activities to be highly variable. However, for each peptide, the individual degradation patterns were quite similar. The metabolic stability of the investigated CPPs was in the order of CF-SAP = CF-hCT(9-32)-br , [Pbeta]-IAF , [Palpha] and we identified specific cleavage sites for each of the ...
Modulating signaling pathways for research and therapy requires either suppression or expression of selected genes or internalization of proteins such as enzymes, antibodies, nucleotide binding proteins or substrates including nucleoside phosphates and enzyme inhibitors. Peptides, proteins and nucleotides are transported by fusing or conjugating them to cell penetrating peptides or by formation of non-covalent complexes. The latter is often preferred because of easy handling, uptake efficiency and auto-release of cargo into the live cell. In our studies complexes are formed with labeled or readily detectable cargoes for qualitative and quantitative estimation of their internalization. Properties and behavior of adhesion and suspension vertebrate cells as well as the protozoa Leishmania tarentolae are investigated with respect to proteolytic activity, uptake efficiency, intracellular localization and cytotoxicity. Our results show that peptide stability to membrane-bound, secreted or intracellular
Patients on BETH :. The LVEF monitoring sequence required by CADY will be altered to parallel that required by BETH. Thus, echocardiograph or MUGA will be carried out according to the BETH cardiac safety monitoring protocol. This altered schedule applies only to patients enrolled in both studies. Of note, for patients on the BETH study, all LVEF assessments must be performed by the same method used at baseline.. Patients on ALTTO:. It is possible that a patient who is enrolled on both CADY and ALLTO may not eventually receive Trastuzumab. Nonetheless, as Lapatinib is also associated with a risk of cardiotoxicity, such patients should remain on study whilst receiving single agent Lapatinib. The schedule of on study assessments will be identical to that of patients receiving Trastuzumab.. For patients enrolled in both studies, the LVEF monitoring sequence required by CADY will be altered to parallel that required by ALLTO. Thus, echocardiograph or MUGA will be carried out according to the ALLTO ...
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© 2015 Elsevier B.V. Oligonucleotide-based drugs have received considerable attention for their capacity to modulate gene expression very specifically and as a consequence they have found applications in the treatment of many human acquired or genetic diseases. Clinical translation has been often hampered by poor biodistribution, however. Cell-penetrating peptides (CPPs) appear as a possibility to increase the cellular delivery of non-permeant biomolecules such as nucleic acids. This review focuses on CPP-delivery of several classes of oligonucleotides (ONs), namely antisense oligonucleotides, splice switching oligonucleotides (SSOs) and siRNAs. Two main strategies have been used to transport ONs with CPPs: covalent conjugation (which is more appropriate for charge-neutral ON analogues) and non-covalent complexation (which has been used for siRNA delivery essentially). Chemical synthesis, mechanisms of cellular internalization and various applications will be reviewed. A comprehensive coverage of the
One oligonucleotide-based approach that appear very promising for the treatment of different genetic disorders are based on so-called splice-correcting oligonucleotides (SCOs) that are exploited to manipulate splicing patterns. In order to increase the bioavailability, cell-penetrating peptides (CPPs) have readily been covalently conjugated to SCOs to facilitate cellular internalization. While being a successful strategy for the delivery of uncharged oligonucleotides (ONs), it is extremely difficult to generate covalent conjugates between commonly used negatively charged ON analogs and cationic CPPs. Furthermore, high concentrations of ONs in the micromolar range are often needed to obtain biological responses, most likely as a result of endosomal entrapment of material. Therefore, exploring other vectorization methods using CPPs with endosomolytic properties are highly desired.A method of using stearyl modified CPP (i.e., TP10) analogs, named PepFect3 and PepFect4, are being described for the
Maurocalcine (MCa), initially identified from a Tunisian scorpion venom, defines a new member of the family of cell penetrating peptides by its ability to efficiently cross the plasma membrane. The initiating mechanistic step required for the cell translocation of a cell penetrating peptide implicates its binding onto cell surface components such as membrane lipids and/or heparan sulfate proteoglycans. Here we characterized the interaction of wild-type MCa and MCa K20A, a mutant analogue with reduced cell-penetration efficiency, with heparin (HP) and heparan sulfates (HS) through surface plasma resonance. HP and HS bind both to MCa, indicating that heparan sulfate proteoglycans may represent an important entry route of the peptide. This is confirmed by the fact that (i) both compounds bind with reduced affinity to MCa K20A and (ii) the cell penetration of wild-type or mutant MCa coupled to fluorescent streptavidin is reduced by about 50% in mutant Chinese hamster ovary cell lines lacking either all
Glycosaminoglycans (GAGs) contribute to the cellular uptake of cationic cell-penetrating peptides (CPPs). However, molecular details about the contributions of GAGs in CPP internalization remain unclear. In this study, we examined the cellular uptake mechanism of the arginine-rich CPP pituitary adenylate-cyclase-activating polypeptide (PACAP). We observed that the uptake efficacy of PACAP is dependent on the expression of cell surface GAGs. As the binding of PACAP to sulfated GAGs induced a random coil-to-α-helix conformational conversion, we investigated the role of the helical formation in PACAP internalization. Whereas this secondary structure was not crucial for efficient internalization in GAGs-deficient cells, PACAP α-helix was essential for GAGs-dependent uptake.. ...
Protein transduction domains (PTDs) are powerful nongenetic tools that allow intracellular delivery of conjugated cargoes to modify cell behavior. Their use in biomedicine has been hampered by inefficient delivery to nuclear and cytoplasmic targets. Here we overcame this deficiency by developing a series of novel fusion proteins that couple a membrane-docking peptide to heparan sulfate glycosaminoglycans (GAGs) with a PTD. We showed that this GET (GAG-binding enhanced transduction) system could deliver enzymes (Cre, neomycin phosphotransferase), transcription factors (NANOG, MYOD), antibodies, native proteins (cytochrome C), magnetic nanoparticles (MNPs), and nucleic acids [plasmid (p)DNA, modified (mod)RNA, and small inhibitory RNA] at efficiencies of up to two orders of magnitude higher than previously reported in cell types considered hard to transduce, such as mouse embryonic stem cells (mESCs), human ESCs (hESCs), and induced pluripotent stem cells (hiPSCs). This technology represents an ...
The increasing prevalence of multidrug-resistant bacteria urges the development of new antibacterial agents. With a broad spectrum activity, antimicrobial peptides have been considered potential antibacterial drug leads. Using bioinformatic tools we have previously shown that viral structural proteins are a rich source for new bioactive peptide sequences, namely antimicrobial and cell-penetrating peptides. Here, we test the efficacy and mechanism of action of the most promising peptides among those previously identified against both Gram-positive and Gram-negative bacteria. Two cell-penetrating peptides, vCPP 0769 and vCPP 2319, have high antibacterial activity against S. aureus, MRSA, E. coli and P. aeruginosa, being thus multifunctional. The antibacterial mechanism of action of the two most active viral protein-derived peptides, vAMP 059 and vCPP 2319, was studied in detail. Both peptides act on both Gram-positive S. aureus and Gram-negative P. aeruginosa, with bacterial cell death occurring within
TGF-β is considered a master switch in the pathogenesis of organ fibrosis. The primary mediators of this activity are the SMAD proteins, particularly SMAD3. In the current study, we have developed a cell-penetrating peptide (CPP) conjugate of the HIV TAT protein that is fused to an aminoterminal sequence of sorting nexin 9 (SNX9), which was previously shown to bind phosphorylated SMAD3 (pSMAD3). We determined that specifically preventing the nuclear import of pSMAD3 using the TAT-SNX9 peptide inhibited profibrotic TGF-β activity in murine cells and human lung fibroblasts as well as in vivo with no demonstrable toxicity. TGF-β signaling mediated by pSMAD2, bone morphogenetic protein 4 (BMP4), EGF, or PDGF was unaffected by the TAT-SNX9 peptide. Furthermore, while the TAT-SNX9 peptide prevented TGF-βs profibrotic activity in vitro as well as in 2 murine treatment models of pulmonary fibrosis, a 3-amino acid point mutant that was unable to bind pSMAD3 proved ineffective. These findings ...
TGF-β is considered a master switch in the pathogenesis of organ fibrosis. The primary mediators of this activity are the SMAD proteins, particularly SMAD3. In the current study, we have developed a cell-penetrating peptide (CPP) conjugate of the HIV TAT protein that is fused to an aminoterminal sequence of sorting nexin 9 (SNX9), which was previously shown to bind phosphorylated SMAD3 (pSMAD3). We determined that specifically preventing the nuclear import of pSMAD3 using the TAT-SNX9 peptide inhibited profibrotic TGF-β activity in murine cells and human lung fibroblasts as well as in vivo with no demonstrable toxicity. TGF-β signaling mediated by pSMAD2, bone morphogenetic protein 4 (BMP4), EGF, or PDGF was unaffected by the TAT-SNX9 peptide. Furthermore, while the TAT-SNX9 peptide prevented TGF-βs profibrotic activity in vitro as well as in 2 murine treatment models of pulmonary fibrosis, a 3-amino acid point mutant that was unable to bind pSMAD3 proved ineffective. These findings ...
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Gene therapy is an approach that introduces nucleic acids into cells and aims to correct the gene function by altering the gene expression to prevent, halt, or reverse a pathological process (1). There are three main routes to gene therapy: restoring a lost gene function, silencing the disease-causing genes, or modifying a gene function. Achieving expression of a deficient gene product by therapeutic gene delivery is considered to be the classical gene therapy approach, but gene silencing and function modification have also gained quite an interest recently. RNA interference (RNAi) is a fundamental gene silencing pathway in eukaryotic cells, which is mediated by short interfering RNA (siRNAs) that can cleave complementary mRNA sequences with the help of the RNA-induced silenci ...
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Cell-penetrating peptides (CPPs), often vividly termed as the "Trojan Horse" peptides, have attracted considerable interest for the intracellular delivery of a wide range of cargoes, such as small molecules, peptides, proteins, nucleic acids, contrast agents, nanocarriers and so on. Some preclinical and clinical developments of CPP conjugates demonstrate their promise as therapeutic agents for drug discovery. There is increasing evidence to suggest that CPPs have the potential to cross several bio-barriers (e. g., blood-brain barriers, intestinal mucosa, nasal mucosa and skin barriers). Despite revolutionary process in many aspects, there are a lot of basic issues unclear for these entities, such as internalization mechanisms, translocation efficiency, translocation kinetics, metabolic degradation, toxicity, side effect, distribution and non-specificity. Among them, non-specificity remains a major drawback for the in vivo application of CPPs in the targeted delivery of cargoes. So far, diverse ...
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Dan Duray had the news on Friday of the latest big-money lawsuit in the New York art world: dealer Marc Jancou is suing Sothebys and artist Cady Noland for $26 million.. The lawsuit is here, and theres absolutely no indication whatsoever of where the $26 million number comes from; I suspect its just an attempt to make a splash in the press. Jancou had consigned a Noland work to Sothebys, which slapped an estimate of $250,000 to $350,000 on it. But then Noland "apparently disavowed the work," according to Baer Faxt - and as a result, Sothebys pulled it from their auction. Jancous upset, and is on the legal warpath.. I see no fault of Sothebys here - if I were in their shoes, Id do the exact same thing. Sothebys clearly has - or had - a good relationship with Jancou: according to the consignment agreement attached to the complaint, they were charging him zero sellers commission, and neither were they charging him for things like insurance, catalogue illustration, packing, and shipping, ...
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Contributing factors for the antimicrobial activity enhancement of N-terminally engineered mutants of cell-penetrating apidaecins were analyzed based on their cell-penetration efficiency. The flow cytometric analysis of the engineered apidaecins labe
Cell-penetrating peptides (CPPs) have attracted great interest as delivery vehicles in medicine, with potential for the development of novel therapeutic agents or cosmetic products. Biological membranes are typically impermeable ...
Delivering peptide-based drugs to the brain is a major challenge because of the existence of the blood-brain barrier (BBB). To overcome this problem, cell-penetrating peptides derived from proteins that are able to cross biological membranes have been used as cell-permeable and brain-penetrant compounds. An example is the transactivator of transcription protein transduction domain (Tat) of the human immunodeficiency virus. The basic domain of Tat is formed of arginine and lysine amino acid residues. Tat has been used as brain-penetrant carrier also in therapies for Alzheimer disease (AD), the most common form of dementia characterized by extracellular cerebral deposits of amyloid made up of Aβ peptide ...
Efficient delivery of heterologous molecules for treatment of cells is a great challenge in modern medicine and pharmacology. Cell penetrating peptides (CPPs) may improve efficient delivery of a wide range of macromolecular cargos including plasmid DNA, small interfering RNA, drugs, nanoparticulate pharmaceutical carriers and anticancer drugs. In this paper, we present history of CPPs discovery with a special attention drawn to sequences of viral origin. We also describe different CPP families with regard to their physicochemical properties and numerous mechanisms of CPP cell uptake by direct penetration and endocytotic pathways. A detailed description is focused on formation of carrier-cargo complexes, which are needed for practical use of CPP in medicine and biotechnology. Examples of successful application of CPPs in treatment of human diseases are also presented, including decreased tumor growth and induction of cancer cell death. Finally, we review modern design approaches to novel CPPs ...
is a major cause of pores and skin and soft cells infections in friend animals and offers zoonotic potential. good antimicrobial activity with MIC50 of 4 μM and MIC90 of 8 μM. Penetratin and (KFF)3K (two cell penetrating peptides) were the least effective with MIC50 of 8 μM and MIC90 of 16 μM. Killing kinetics revealed a major advantage of peptides over standard antibiotics demonstrating potent bactericidal activity within minutes. Studies with propidium iodide and transmission electron microscopy exposed that peptides damaged the bacterial membrane leading to leakage of cytoplasmic material and consequently cell death. A potent synergistic increase in the antibacterial effect of the cell penetrating IL27RA antibody peptide (KFF)3K was noticed when combined with additional peptides and with antibiotics. In addition all peptides displayed synergistic relationships when combined collectively. Furthermore peptides shown good restorative indices with minimal toxicity toward mammalian cells. ...
1166 Tumor cell metastasis is a complex, multi-step process that is a major cause of morbidity and death amongst cancer patients. Cell adhesion plays a critical role in the development of metastatic cancer, and it is mediated by interactions between receptors on the cell surface and ligands of the extracellular matrix or other surfaces. Therefore, inhibition of the cell adhesion process appears to be an effective method of preventing metastasis. To prevent cell adhesion, we developed genetically engineered polypeptides with the potential to inhibit metastases. We have found that the cell penetrating peptides (CPP) Tat or penetratin (Pen), fused with elastin-like polypeptide (CPP-ELP) inhibited adhesion, spreading, invasion and migration of SKOV-3 ovarian cancer cells, SK-MEL-2 melanoma cells, and MDA-MB-231 breast cancer cells in cell culture. Furthermore, we have also confirmed that Tat-ELP has anti-metastatic potential in an experimental ovarian cancer metastasis model in vivo. Therefore, ...
Quyen Nguyen and colleagues at the University of California have developed a probe that can be used to study thrombin activity in coagulation and atherosclerosis.. The probe was used in vivo to image atherosclerotic plaques in living mice. The fluorescent probe is based on an activatable cell penetrating peptide (ACPP) that incorporates a peptide sequence from the proteinase activated receptor 1. The probe is preferentially cleaved by thrombin (cleavage can be blocked using thrombin inhibitors), and this fluorescent cleavage product builds up at the site of atherosclerotic lesions. The fluorescence intensity varies depending on the severity of the plaque and the histologic grade of the aorta.. The probe was also used with human atheroma specimens ex vivo, and the retention of the fluorescent cleavage product was 63% higher than that found when using a control ACPP.. The team hope that probes like this could eventually be used to deliver MRI contrast agents to atherosclerotic plaques to enable ...
Publications COLUMBIA UNIVERSITY (28 TOTAL) Kang, W.H., Simon, M.J., Gao, S., Banta, S., and Morrison III, B. (2011) "Attenuation of astrocyte activation by TAT mediated delivery of a peptide JNK inhibitor" Journal of Neurotrauma (In Press). Kim, Y.H., and Banta, S. (2011) "A self-assembling hydrogel created from three modified dehydrogenases enables the complete oxidation of methanol in an enzymatic biofuel cell" Angewandte Chemie International Edition (In Press). (Recognized as VIP publication) Szilvay, G.R., Brocato, S., Ivnitski, D., Li, C., DeLa Iglesia, P., Lau, C., Chi, E., Werner-Washburne, M., Banta, S., and Atanassov, P. (2011) "Engineering of a redox protein for DNA-directed assembly" Chemical Communications (In Press) Gao, S., Simon, M.J., Hue, C.D., Morrison III, B., and Banta, S. (2011) "An unusual cell penetrating peptide identified using a plasmid display-based functional selection platform" ACS Chemical Biology (In Press). (Recommended by Faculty of 1000, Featured in ...
This database maintains therapeutically and functionally important cell penetrating peptide sequences and their secondary and tertiary structure.
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Crystal has every single holiday Barbie doll since they debuted in 1988. Cant live without: Sirius Satellite First Wave Radio. ""My goal is to see all of my favorite bands...that I was way too little to see in the 80s."". ...
The goal of this research is to develop an economical, safe, effective therapy to reverse the activity of the catalytic component, LF, of the Bacillus anthracis...
Sigma-Aldrich offers abstracts and full-text articles by [Sabrina Höfling, Julia Scharnert, Christoph Cromme, Jessica Bertrand, Thomas Pap, M Alexander Schmidt, Christian Rüter].
CPPs have for numerous years been utilized as delivery vectors of various pharmaceutically interesting cargoes, both in vitro and in vivo. As CPPs are gradually approaching the bedsides, investigating toxicity associated with these highly interesting peptides becomes increasingly important and thorough initial assessment of cytotoxicity in vitro is a first step towards advancing these delivery vehicles in to the clinics. The present chapter describes protocols for four cytotoxicity assays in order to provide a toolbox for toxicity assessment of CPPs. The foci lie on membrane integrity (deoxyglucose leakage and propidium iodide assays) and cell viability (the MTT assay), but the chapter also provides a protocol for assessing an important parameter for future clinical applications, namely the hemolytic properties of CPPs.
Physical properties, such as surface charge, of nanomedicines play a crucial role in their in vivo behaviors, which could eventually determine the tumor inhibition effect. Although drug delivery systems with positive charge are effective for cell internalization, this property is universally applicable to th
Background Systemic delivery of little interfering RNA (siRNA) is normally limited by its poor stability and limited cell-penetrating properties. to condense siRNA and to defend it from destruction by nucleases, as verified by serum electrophoresis. siRNA delivery mediated by PEI-AAV2-VLPs lead in a high transfection price in MCF-7 breasts cancer tumor cells with no significant […]. ...
Recombinant protein or peptide? - posted in Protein Expression and Purification: I am researching the role of the 18-amino acid cytoplasmic domain of a transmembrane receptor. I want to do a couple things: 1) screen cell lysates to see which proteins associate with this cytoplasmic domain, 2) transduce the cytoplasmic domain into cells via a cell-penetrating TAT sequence to determine if it is inhibitory (by sequestering binding proteins from the endogenous receptor). I have several questi...
Polyplus-transfection® has developed a novel class of cationic modified oligonucleotides (OLIGOPLUS) that require no delivery agent as they act as cell-penetrating oligonucleotides. This is achieved by grafting cationic spermine units onto the oligonucleotide to create a positively charged oligocation-oligonucleotide conjugate.
van Belkum, A and Soriaga, LB and LaFave, MC and Akella, S and Veyrieras, J-B and Barbu, EM and Shortridge, D and Blanc, B and Hannum, G and Zambardi, G and Miller, K and Enright, MC and Mugnier, N and Brami, D and Schicklin, S and Felderman, M and Schwartz, AS and Richardson, TH and Peterson, TC and Hubby, B and Cady, KC ...
The Nineteenth Amendments text was drafted by Susan B. Anthony with the assistance of Elizabeth Cady Stanton. The proposed amendment was first introduced in the U.S. Senate colloquially as the "Anthony Amendment", by Senator Aaron A. Sargent of California. Sargent, who had met and befriended Anthony on a train ride in 1872, was a dedicated womens suffrage advocate. He had frequently attempted to insert womens suffrage provisions into unrelated bills, but did not formally introduce a constitutional amendment until January 1878. Stanton and other women testified before the Senate in support of the amendment. The proposal sat in a committee until it was considered by the full Senate and rejected in a 16 to 34 vote in 1887.. A three-decade period known as "the doldrums" followed, during which the amendment was not considered by Congress and the womens suffrage movement achieved few victories. During this period, the suffragists pressed for the right to vote in the laws of individual states and ...
Weber, RS, Abemayor, E, Adams, GL, Adelstein, DJ, Alavi, A, Alford, E, Al-Sarraf, M, Alvi, A, Ambinder, R, Amdur, R, Amedee, RG, Anand, VK, Andersen, P, Anderson, T, Ang, KK, Antonelli, PJ, Ariyan, S, Aviv, JE, Ayala, A, Baatenburg de Jong, RJ, Backous, D, Bailey, BJ, Baker, S, Baloch, ZW, Barnes, EL, Barrera, J, Bastian, R, Batsakis, JG, Bauman, N, Becker, D, Beenken, S, Beitler, JJ, Berke, G, Blacklock, JB, Blackwell, K, Blitzer, A, Blom, E, Bolger, WE, Bone, RC, Boyd, J, Boyd, D, Boyle, J, Braakhuis, B, Bradford, C, Bradley, PJ, Brakenhoff, R, Breitbart, W, Brizel, D, Brock, WA, Brown, RE, Brown, A, Buatti, J, Burgess, MA, Burkey, B, Busse, P, Byers, RM, Cabanillas, F, Cady, B, Calcaterra, T, Calhoun, K, Califano J. J, Callender, DL, Campbell, BH, Carew, J, Carey, T, Carey, TE, Carrau, RL, Carroll, WR, Cassisi, NJ, Chalian, AA, Charous, S, Chen, A, Cheney, M, Cheville, A, Chonkich, G, Chonkick, G, Civantos, F, Clark, KF, Clayman, G, Close, LG, Cohen, JI, Coleman, JJ, Coleves, AD, Coltrera, ...
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Identification of a cell-penetrating peptide domain from human beta-defensin 3 and characterization of its anti-inflammatory activity Jue Yeon Lee,1,* Jin Sook Suh,2,* Jung Min Kim,1 Jeong Hwa Kim,1 Hyun Jung Park,1 Yoon Jeong Park,1,2 Chong Pyoung Chung1 1Central Research Institute, Nano Intelligent Biomedical Engineering Corporation (NIBEC), Chungcheongbuk-do, Republic of Korea; 2Dental Regenerative Biotechnology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea *These authors contributed equally to this work Abstract: Human beta-defensins (hBDs) are crucial factors of intrinsic immunity that function in the immunologic response to a variety of invading enveloped viruses, bacteria, and fungi. hBDs can cause membrane depolarization and cell lysis due to their highly cationic nature. These molecules participate in antimicrobial defenses and the control of adaptive and innate immunity in every mammalian species and are produced by various cell
Publisher: University of Delaware. Date Issued: 2015. Abstract: Structural mechanisms and underlying thermodynamic determinants of efficient internalization of charged cationic peptides (cell-penetrating peptides, CPPs) such as TAT, polyarginine, and their variants, into cells, cellular constructs, and model membrane/lipid bilayers (large and giant unilamellar or multilamelar vesicles) continue to garner significant attention. Two widely-held views on the translocation mechanism center on endocytotic and non-endocytotic (diffusive) processes. Using the translocation of short, charged cationic oligo-arginine peptides (mono-, di-, and tri-arginine) from bulk aqueous solution into model DMPC bilayers, we explore the question of the similarity of thermodynamic and structural predictions obtained from molecular dynamics simulations using all-atom and the Martini coarse-grain force fields. Specifically, we estimate potentials of mean force associated with translocation using standard all-atom ...
Zuschriften DOI: 10.1002/ange.201104514 Delivery Platforms Oligonucleotide Delivery by Cell-Penetrating "Striped" Nanoparticles** Christopher M. Jewell, Jin-Mi Jung, Prabhani U. Atukorale, Randy P. Carney, Francesco Stellacci,* and Darrell J. Irvine* Gold nanoparticles (AuNPs) hold great interest in drug delivery because these materials can be functionalized with a range of biological cargos, induce minimal toxicity, and can be efficiently cleared from the body.[1] For example, many studies have described conjugation of DNA or RNA to particle surfaces in well-defined configurations, and these materials have been applied in numerous biological and therapeutic settings.[1, 2] Devising new ways to mediate cell entry by AuNPs is a central area of interest. When mixed self-assembled monolayers of dislike molecules are used to coat AuNPs, nanoscale domains spontaneously form in the particles ligand shell. In particular, "stripe-like" domains form for ca. 1:1 binary mixed ligand compositions.[3] The ...
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Frank Cady, character actor, dies at 96; Don Campbell, author, dies at 65; Frank Arciero, developer, dies at 86; F. Herbert Bormann, acid rain discoverer, dies at 90
A novel solid-state NMR technique for identifying the asymmetric insertion depths of membrane proteins in lipid bilayers is introduced. By applying Mn2+ ions on the outer but not the inner leaflet of lipid bilayers, the sidedness of protein residues in the lipid bilayer can be determined through paramagnetic relaxation enhancement (PRE) effects. Protein-free lipid membranes with one-side Mn2+-bound surfaces exhibit significant residual 31P and lipid headgroup 13C intensities, in contrast to two-side Mn2+-bound membranes, where lipid headgroup signals are mostly suppressed. Applying this method to a cell-penetrating peptide, penetratin, we found that at low peptide concentrations, penetratin is distributed in both leaflets of the bilayer, in contrast to the prediction of the electroporation model, which predicts that penetratin binds to only the outer lipid leaflet at low peptide concentrations to cause an electric field that drives subsequent peptide translocation. The invalidation of the ...
Cellular introduction of PEBBLEs (photonic explorers for bioanalysis with biologically localized embedding) has been investigated by a wide variety of methods in a range of cell types. These methods include surface functionalization with CPPs (cell-penetrating peptides), pinocytosis, commercial lipid transfection agents, cytochalasin D, picoinjection, and Gene gun bombardment. This paper will overview several of the most popular methods used for the introduction of PEBBLE nanosensors to the cellular environment and discuss the efficacy of the techniques.. ...
This is a short cell-penetrating peptide (CPP) derived from the venom peptide of Tunician scorpion. It can permeate cell membrane at low micromolar concentration in minutes without significantly affecting cell membrane. Maurocalcine can be conjugated with large molecules and used as a drug delivery vehicle.
In recent years, significant research efforts have been dedicated to improving the treatment options and visual outcomes of patients with age-related macular degeneration (AMD). The introduction of VEGF inhibitors offered a means of preventing permanent vision loss, and even improving vision. However, the necessity of monthly or bimonthly intravitreal injections still remains. Presentations at ARVO 2015 highlighted several novel delivery systems in development to address this limitation.. DeCogan et al presented a de novo-designed system of cell-penetrating peptide constructs fused to a therapeutic protein transduction domain (DeCogan F: 4147). In vivo, the system successfully transported microgram quantities of macromolecules, such as the large monoclonal VEGF inhibitors, in a topically administered drop that penetrated to the back of the eye.. Other presentations focused on slow-release depots of VEGF inhibitors. Initial in vitro pharmacokinetic work was presented on controlled-release polymer ...
A Short Region of Connexin43 Reduces Human Glioma Stem Cell Migration, Invasion, and Survival through Src, PTEN, and FAK The authors showed that a cell-penetrating peptide based on CX43 inhibited c-Src and focal adhesion kinase (FAK) and upregulated phosphatase and tensin homolog in glioma stem cells derived from patients. [Stem Cell Reports] Full Article BAG3 Promotes Stem Cell-Like Phenotype in Breast Cancer by Upregulation of CXCR4 via Interaction with its Transcript Scientists reported that BAG3 was induced under specific floating culture conditions that enrich breast CSC-like cells in spheres. Ectopic BAG3 overexpression increased CD44+/CD24− CSC subpopulations, first-generation and second-generation mammosphere formation, indicating that BAG3 promotes CSC self-renewal and maintenance in breast cancer. [Cell Death Dis] Full Article Aptamer-Mediated Survivin RNAi Enables 5-Fluorouracil to Eliminate Colorectal Cancer Stem Cells Researchers showed that EpCAM-aptamer-guided survivin RNAi ...
In this dissertation, a novel cell penetrating peptide (CPP)-based polyplex was developed and evaluated for small interfering RNA (siRNA) delivery and efficacy. The design resolved the CPP carrier neutralization issue, where CPP cellular uptake is compromised by electrostatic interactions between the CPP and siRNA, by using a chemically modified 21mer oligolysine (K21-PDP) to form a stable and neutralized polyplex with siRNA. This neutralized polyplex served as a suitable platform to conjugate distinct CPP carrier moieties - cationic (hexaarginine, R6) and amphipathic (model amphipathic peptide, MAP) - to determine which CPP property was more suitable for siRNA delivery. Since K21-PDP already effectively neutralized the siRNA, the CPP carriers on the conjugated CPP-polyplexes, R6-polyplex and MAP-polyplex, were able to function without electrostatic interference. Amphipathic MAP was found to be a better CPP carrier than R6 because MAP-polyplex exhibited greater siRNA intracellular uptake and ...
Neurological diseases such as neurodegeneration, pain, psychiatric disorders, stroke, and brain cancers would greatly benefit from the use of highly potent and specific peptide pharmaceuticals. Peptides are especially desirable because of their low inherent toxicity. The presence of the blood brain barrier (BBB), their short duration of action, and their need for parenteral administration limits their clinical use. However, over the past decade there have been significant advances in delivering peptides to the central nervous system. Angiopep peptides developed by Angiochem (Montreal, Canada), transferrin antibodies developed by ArmaGen (Santa Monica, USA), and cell penetrating peptides have all shown promise in delivering therapeutic peptides across the BBB after intravenous administration. Noninvasive methods of delivering peptides to the brain include the use of chitosan amphiphile nanoparticles for oral delivery and nose to brain strategies. The uptake of the chitosan amphiphile ...
Ashwanikumar et al have developed a drug delivery system using cell-penetrating self-assembling peptide nanomaterials (CSPNs); these drilled-shaped nanomaterials traverse cellular membranes to deliver drugs and can be fine-tuned into different shapes to optimize delivery. Image credit: Ashwanikumar et al, doi: 10.1016/j.jconrel.2018.02.041.. Developing effective therapeutic drugs is an arduous process that involves a large investment of time and money even before clinical trials begin.. Often, drugs that should theoretically treat a disease do not reach clinical trials because the drugs fail to penetrate biological barriers such as cellular membranes and reach the desired molecular target.. Scientists at Oregon State University have developed a new nanomaterial that facilitates the delivery of drugs through cell membrane which they call CSPNs, or cell-penetrating self-assembling peptide nanomaterials.. Composed of amino acids that self-assemble into a shape akin to a drill bit, these ...
We were pleased to welcome Dr. Blake Cady as our visiting professor and judge. Drs. Desmond Birkett, Patricia Donahoe, and Steven Schwaitzberg joined him as judges. This year there were many more submissions than could be presented today demonstrating the continued enthusiasm for surgical research here in New England. ...
Cady here. Im glad Mommy and Daddy got a weekend away. I know they really needed it. Mom said she was going on vacation and I was getting a Stay-cation. Im not totally sure what that it, but I know I like it and Mommy and Daddy can go away like that any time. Nana…
SS Pauliah, PJ Lally, DL Price, A Bainbridge, J Kurien, N Sivaswami, FM Cowan, G Balraj, R Swamy, V Madhavan, M Nair, P Krishnakumar, EB Cady, S Shankaran, S Thayyil ...
Sigma-Aldrich offers abstracts and full-text articles by [M Lahn, H Kalataradi, P Mittelstadt, E Pflum, M Vollmer, C Cady, A Mukasa, A T Vella, D Ikle, R Harbeck, R OBrien, W Born].
Over the next number of weeks, Brian Cady will be joined on "Cadys Corner" every Saturday morning at around 10:15 by a representative from the Capital District Basketball Association, the only NCAA-sanctioned summer league in the Capital Region and one of only about 70 in the entire count ...
C. M. Jewell, Jung, J. - M., Atukorale, P. U., Carney, R. P., Stellacci, F., and Irvine, D. J., "Oligonucleotide Delivery by Cell-Penetrating "Striped" Nanoparticles", Angewandte Chemie-International Edition, vol. 50, no. 51, pp. 12312 - 12315, 2011. ...
C. M. Jewell, Jung, J. - M., Atukorale, P. U., Carney, R. P., Stellacci, F., and Irvine, D. J., "Oligonucleotide Delivery by Cell-Penetrating "Striped" Nanoparticles", Angewandte Chemie-International Edition, vol. 50, no. 51, pp. 12312 - 12315, 2011. ...
Recent breakthroughs in gene editing have necessitated practical ex vivo methods to rapidly and efficiently re-engineer patient-harvested cells. Many physical membrane-disruption or pore-forming techniques for intracellular delivery, however, result in poor cell viability, while most carrier-mediated techniques suffer from suboptimal endosomal escape and hence cytoplasmic or nuclear targeting. In this work, we show that short exposure of cells to high frequency (>10 MHz) acoustic excitation facilitates temporal reorganisation of the lipid structure in the cell membrane that enhances translocation of gold nano- particles and therapeutic molecules into the cell within just ten minutes. Due to its transient nature, rapid cell self-healing is observed, leading to high cellular viabilities (>97%). Moreover, the internalised cargo appears to be uniformly distributed throughout the cytosol, circumventing the need for strategies to facilitate endosomal escape. In the case of siRNA delivery, the method ...
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In order to achieve more effective targeted delivery of macromolecular drugs (proteins, nucleic acids, polymer-drug conjugates), targeting and activation of therapeutic component (i.e., triggered release) are combined. The term ATTEMPTS (Antibody Targeted, Triggered, Electrically Modified Prodrug Type Strategy) began with the system for delivery of thrombolytic enzyme (t-PA) with the aid of an antibody. Each component is conjugated to oppositely charged entities (+ charged peptides on the t-PA and heparin on the antibody) and allowed to form complexes via electrostatic interaction. Once reaching the target site, a triggering agent (i.e., protamine) is administered to release the therapeutic component so that it will act on the target. This concept is not just limited to the delivery of thrombolytic agent using antibody, but now expanded to other applications such as tumor targeting and therapy, with a variety of targeting moiety and arginine-rich cell-penetrating peptide (e.g., low molecular ...
Molecules such as mRNAs have been used for the prevention and treatment of various diseases [18-21], including cancer [18-20]. However, there are several obstacles in the in vivo application of mRNAs, including the low in vivo delivery efficiency of mRNA, their lack of cell-type specificity, and instability. In this study, we introduced a delivery system based on PP7 VLPs and a cell-penetrating peptide as a solution to the above limitations of mRNA-targeted delivery.. In order to improve the delivery efficiency of mRNA, the PP7 VLPs were decorated with a non-toxic cell-penetrating peptide, LMWP. This peptide, similar to the peptide TAT, enhanced the intracellular delivery of the linked particles without any dependence on receptors, temperature conditions, or energy use and without causing any alterations to the cell membrane [22-24]. The cell-penetrating assay showed that the LMWP peptide was displayed on the surface of PP7 VLPs.. Previous studies have shown that MS2 capsids specifically ...
This is the # 1 site for hypnosis entertainment, hypnosis shows, hypnotists and hypnotherapy in the United States. Hypnotist chris cady performs his hypnosis comedy shows, for corporate, college, conventions, casinos, high school gradnights christmas parties, other entertainment and special events all over the USA including California, Reno, Las Vegas Nevada, Washington, San Francisco, San Jose, Sacremento, Los Angeles and more. He is also a sports hypnotist specializing in working with athletes on the mental game using hypnosis.
Introduction: The utility of recombinant proteins as potential therapeutics and cellular tools are largely impeded by endosome entrapment and susceptibility of delivered proteins in lysositic environments and degradative enzymes. We describe a modular, light-activated nanocarrier that transports proteins into cells by receptor-mediated endocytosis, and deliver the cargo to the cytosol by light triggered endosomal escape in a timely manner. The delivery platform is based on plasmonic hollow gold nanoshells (HGN) assembled with a cargo linking layer based on nickel affinity capable of supporting virtually any soluble poly-histidine tagged proteins. Transport into endosomes is mediated by the fusion of cell-penetrating peptides onto the protein of interest or by presenting an orthogonal internalizing handle. Once internalized, cytosolic localization of the protein of interest is achieved by excitation of nanocarriers with pulsed near-infrared (NIR) light to trigger protein release and disruption of ...
We report the formulation of novel composite nanoparticles that combine the high transfection efficiency of cationic peptide-DNA nanoparticles with the biocompatibility and prolonged delivery of polylactic acid-polyethylene glycol (PLA-PEG). The cationic cell-penetrating peptide RALA was used to condense DNA into nanoparticles that were encapsulated within a range of PLA-PEG copolymers. The composite nanoparticles produced exhibited excellent physicochemical properties including size |200 nm and encapsulation efficiency |80%. Images of the composite nanoparticles obtained with a new transmission electron microscopy staining method revealed the peptide-DNA nanoparticles within the PLA-PEG matrix. Varying the copolymers modulated the DNA release rate |6 weeks in vitro. The best formulation was selected and was able to transfect cells while maintaining viability. The effect of transferrin-appended composite nanoparticles was also studied. Thus, we have demonstrated the manufacture of composite
Controlled release systems for therapeutic molecules are vital to allow the sustained local delivery of their activities which direct cell behaviour and enable novel regenerative strategies. Direct programming of cells using exogenously delivered transcription factors can by-pass growth factor signalling but there is still a requirement to deliver such activity spatio-temporally. We previously developed a technology termed GAG-binding enhanced transduction (GET) to efficiently deliver a variety of cargoes intracellularly, using GAG-binding domains which promote cell targeting, and cell penetrating peptides (CPPs) which allow cell entry. Herein we demonstrate that GET system can be used in controlled release systems to mediate sustained intracellular transduction over one week. We assessed the stability and activity of GET peptides in poly(dl-lactic acid-co-glycolic acid) (PLGA) microparticles (MPs) prepared using a S/O/W double emulsion method. Efficient encapsulation (∼65%) and tailored ...
Drake University Law School officials and students will have their hands full with a variety of activities in the next few weeks.. Leading off the activities will be the James T. Grant Iowa Constitution Lecture Series presentation by Iowa Supreme Court Justice Brent Appel at 3 p.m. tomorrow (March 27) in Cartwright Hall, Room 206. The title of his presentation is: "State Constitutional Law in Iowa: Past, Present, and Future.". Rounding out the Constitution Lecture Series for this spring will be presentations by Sanford Levinson, law professor of government at the University of Texas, at 4 p.m. Friday (April 5) at the Drake Legal Clinic, and Iowa Supreme Court Chief Justice Mark Cady at 4 p.m. Tuesday (April 8) in Cartwright Hall, Room 213. Professor Levinson will discuss "More Alike Than Different: A Comparison of the U.S. and Iowa Constitutions." Chief Justice Cady will present "A Pioneers Constitution: How Iowas Constitutional History Uniquely Shapes Our Pioneering Tradition in Recognizing ...
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Poursuite des ouvertures en vallée du Cady.. Au menu, des lignes plutôt faciles et classes! Big up Seb pour le brossage et la chasse aux orties
T. Zhu, S. Faulkner, T. Madaan, A. Bainbridge, D. Price, D. Thomas, E. Cady, N. Robertson, X. Golay, and I. Tachtsidis, "Optimal Wavelength Combinations for Resolving in-vivo Changes of Haemoglobin and Cytochrome-c-oxidase Concentrations with NIRS," in Biomedical Optics and 3-D Imaging, OSA Technical Digest (Optical Society of America, 2012), paper JM3A.6 ...
Gallery in Dusseldorf ARTISTS | JAN ALBERS, ANDREA BOWERS, ROBERT CRUMB, GEORGANNE DEEN, NICOLE EISENMAN, SABRINA FRITSCH, MANUEL GRAF, LEROY GRANNIS, GREGOR HILDEBRANDT, KATIE HOLTEN, MARKUS KARSTIESS, JAN KEMPENAERS, ROSILENE LUDUVICO, MARK MENDER, RUSS MEYER, TRACEY MOFFATT, REINHARD MUCHA, CADY NOLAND, MANFRED PERNICE, RUDOLF STEINER, JENS ULLRICH, JOCHEN WEBER, WENDY WHITE, STEFAN WISSEL
Artist and illustrator Cady Driver wrote a touching blog post honoring fathers who have adopted and dads of kids of special needs.
binding enhanced transduction get peptides for sustained and highly efficient intracellular delivery Senate President Susan Wagle said the bill, which was approved Wednesday in the Kansas House, goes beyond protecting religious freedom. She raised concerns about how the measure could impact businesses that would refuse services to gay couples."I believe the intent of the House Read more about Ray Ban Tech Collection[…]. ...
CPP (5[6]-carboxyfluorescein-RRRRRR-COOH) synthesis was performed on a 1-mmol scale on preloaded Fmoc-Nw-(2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl)-L-arginine Wang resin (Sigma-Aldrich, Poole, UK) (loading rate 0.62 mmol g−1) using standard Fmoc-amino acid solid-state peptide synthesis protocols. The initial Fmoc group was removed by deprotection with 20% piperidine in N,N-dimethylformamide (DMF) (3 × 20 minutes), followed by coupling with Fmoc-Nw-(2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl)-L-arginine in the presence of O-(6-chlorobenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HCTU), N,N-diisopropylethylamine (DIPEA), and DMF in a 1:5:5:10 molar ratio. The reaction was agitated at room temperature for 8 hours, and some of the resin was tested for reaction completion using the ninhydrin test following standard protocols.25 The coupling and deprotection steps were repeated until the peptide sequence reached a total of six arginine residues. The final ...
Abstract We designed a delivery system to obtain an efficient and optimal nose-to-brain transport of BACE1 siRNA, potentially useful in the treatment of Alzheimers disease. We selected a cell-penetrating peptide, the short peptide derived from rabies virus glycoprotein known as RVG-9R, to increase the transcellular pathway in neuronal cells. The optimal molar ratio between RVG-9R and BACE1 siRNA was elucidated. The complex between the two was then encapsulated. We propose chitosan-coated and uncoated solid lipid nanoparticles (SLNs) as a nasal delivery system capable of exploiting both olfactory and trigeminal nerve pathways. The coating process had an effect on the zeta potential, obtaining positively-charged nanoparticles, and on siRNA protection. The positive charge of the coating formulation ensured mucoadhesiveness to the particles and also prolonged residence time in the nasal cavity. We studied the cellular transport of siRNA released from the SLNs using Caco-2 as a model of ...
The blood-brain barrier is a substantial obstacle for delivering anticancer agents to brain tumors, and new strategies for bypassing it are sorely needed for brain tumor therapy. Intranasal delivery provides a practical, noninvasive method for delivering therapeutic agents to the brain. Intranasal application of nano-sized micelles that have been modified with Tat peptide facilitates brain delivery of fluorescent model materials. In this study, we evaluated a nose-to-brain delivery system for brain tumor therapy. We nasally administered the anti-tumor drug camptothecin (CPT) in solution and in methoxy poly(ethylene glycol) (MPEG)/poly(e-caprolactone) (PCL) amphiphilic block copolymers (MPEG-PCL) and cell penetrating peptide, Tat analog-modified MPEG-PCL (MPEG-PCL-Tat) MPEG-PCL-Tat to rats bearing intracranial glioma tumors and quantified the cytotoxicity against glioma cells, and the therapeutic effects. CPT-loaded MPEG-PCL-Tat micelles showed higher cytotoxicity than CPT-loaded MPEG-PCL. CPT-free MPEG
http://www.northeastern.edu/research/centers/center-for-pharmaceutical-biotechnology-and-nanomedicine/ View Website » The Center for Pharmaceutical Biotechnology and Nanomedicine is a recently organized research unit aiming to perform studies on the border between two fast growing scientific areas, Biotechnology and Nanomedicine. The missions of the Center include: 1. Intensive research in such areas as Nanomedicine (pharmaceutical nanocarriers with controllable properties for delivery and targeting of water-insoluble drugs, DNA, and diagnostic agents to various disease sites); Intracellular Drug Delivery (the use of cell penetrating peptides for delivery of drugs and DNA directly into the cell cytoplasm bypassing the endocytic pathway and increasing the efficiency of therapies); Experimental Cancer Immunotherapy (the research in the area of tumor-specific antibodies and the use of these antibodies for specific delivery of drugs and diagnostic agents to tumors); Combination Therapy of Cancer ...
Nanostructured lipid carriers (NLC) composed of solid and liquid lipids, and surfactants are potentially good colloidal drug carriers. Before NLC can be us
In order to improve drug entrapment efficiency and loading capacity, nanostructured lipid carriers consisting of solid lipid and liquid lipid as a new type of colloidal drug delivery system were prepared. The dispersions of oridonin-loaded solid lipid nanoparticles and nanostructured lipid carriers were successfully prepared by the emulsion-evaporation and low temperature-solidification technique using monostearin as the solid lipid, caprylic/capric triglycerides as the liquid lipid and oridonin as the model drug. Their physicochemical properties of oridonin-loaded nanostructured lipid carriers and release behaviours were investigated and compared with those of solid lipid nanoparticles. As a result, the mean particle size was similar to 200 nm with narrow polydispersity index lower than 0.4 for all developed formulations. Zeta potential values were in the range -35 mV similar to -50 mV, providing good physical stability of all formulations. The differential scanning calorimetry and X-ray ...
The first target of antimicrobial peptides (AMPs) is the bacterial membrane. In the case of Gram-negative bacteria this is the outer membrane (OM), the lipid composition of which is extremely asymmetric: Whereas the inner leaflet is composed of a phospholipid mixture, the outer leaflet is made up solely from lipopolysaccharides (LPSs). LPS, therefore, represents the first target of AMPs. The binding and intercalation of polycationic AMPs is driven by the number and position of negatively charged groups of the LPS. Also, proteins other than cationic AMPs can interact with LPS, e.g. leading eventually to a neutralization of the endotoxic effects of LPS. We compared different biophysical techniques to gain insight into the properties of the electrical surface potentials of lipid monolayers and aggregates composed of LPSs and various phospholipids and their interaction with peptides and proteins. The net negative charge calculated from the chemical structure of the phospholipid and LPS molecules is linearly
  • Aguilera TA, Olson ES, Timmers MM, Jiang T, Tsien RY (2009) Systemic in vivo distribution of activatable cell penetrating peptides is superior to that of cell penetrating peptides. (springer.com)
  • Activatable cell penetrating peptides linked to nanoparticles as dual probes for in vivo fluorescence and MR imaging of proteases. (nih.gov)
  • We now report in vivo visualization of matrix metalloproteinase activities by MRI and fluorescence of dendrimeric nanoparticles coated with activatable cell penetrating peptides (ACPPs), labeled with Cy5, gadolinium, or both. (nih.gov)
  • Activatable cell penetrating peptides (ACPPs) are novel in vivo targeting agents comprised of a polycationic cell penetrating peptide (CPP) connected via a cleavable linker to a neutralizing polyanion ( Fig. 1A ). (pubmedcentralcanada.ca)
  • However, the crossing of cellular membranes constitutes the principal impediment to gaining entry into cells, and the potential therapeutic application of many drugs is predominantly dependent on the development of delivery tools that should take the drug to target cells selectively and efficiently with only minimal toxicity. (mdpi.com)
  • We determined that specifically preventing the nuclear import of pSMAD3 using the TAT-SNX9 peptide inhibited profibrotic TGF-β activity in murine cells and human lung fibroblasts as well as in vivo with no demonstrable toxicity. (jci.org)
  • Khafagy E-S, Kamei N, Nielsen EJB, Nishio R, Takeda-Morishita M (2013) One-month subchronic toxicity study of cell-penetrating peptides for insulin nasal delivery in rats. (springer.com)
  • As translocation across the plasma membrane is a limiting step for delivery of macromolecules, these polypeptides were utilized in a pancreatic xenograft model to study the plasma clearance, biodistribution, tumor accumulation, and tumor reduction capabilities of the polypeptide with and without a cell-penetrating peptide. (dovepress.com)
  • CPP-mediated cellular uptake can be found from prokaryotic to eukaryotic organisms including mammalian cells, aquatic microorganism, yeasts, insect cells, mice dermis, plant tissue, Gram-negative and Gram-positive bacteria, and archaea. (selfgrowth.com)
  • In addition, cellular uptake of coumarin by rat glioma cells transfected with coumarin-loaded MPEG-PCL or MPEG-PCL-Tat was determined. (springer.com)
  • Cellular uptake of self-assembled cationic peptide-DNA complex: multifunctional role of the enhancer chloroquine. (springer.com)
  • Cell-penetrating peptides are short and basic peptides are widely used due to their ability to deliver a cargo across the membrane both in vitro and in vivo . (mdpi.com)
  • An ACPP cleavable by matrix metalloproteinase-2 (MMP-2) in vitro was the first one demonstrated to work in a tumor model in vivo , but only HT-1080 xenografts and resected human squamous cell carcinomas were tested. (pubmedcentralcanada.ca)
  • A transcriptome in vivo analysis tag (TIVA tag) is a multifunctional, photoactivatable mRNA-capture molecule designed for isolating mRNA from a single cell in complex tissues. (wikipedia.org)
  • Lysates from AKR-2B cells untreated (-) or stimulated (+) for 45 minutes with 5 ng/ml TGF-β were incubated with GST beads or the indicated fusion proteins immobilized on GST beads. (jci.org)
  • With the advance of science and technology, nanomaterials have been seen in various biomedical applications, including molecular labeling and tracking, DNA/RNA/proteins probing, drug delivery and therapies via techniques of biocujugation , tumor or tissue targeting, peptide drug discovery , pathogenic intervention as well as biomedical imaging. (selfgrowth.com)
  • Morris MC, Depollier J, Mery J, Heitz F, Divita G (2001) A peptide carrier for the delivery of biologically active proteins into mammalian cells. (springer.com)
  • This chapter gives an introduction to and discussion of the commonly used production and characterization methods for CPP-cargo samples including high-throughput cell viability screening. (springer.com)
  • This review describes the development of cell-penetrating dendrimers based on several different backbones, their structure-property relationships, and comparisons of their efficacies with those of known cell penetrating peptides. (mdpi.com)
  • Following treatment with or without TGF-β (5 ng/ml) for 1 hour, immunofluorescence for SMAD3 or the HA-tagged TAT peptide was performed as described in Methods and nuclei were stained with DAPI. (jci.org)
  • Dendritic analogues of cell penetrating peptides, with multiple guanidine groups on their peripheries offer advantages as their high symmetry allows them to be efficiently synthesized, while orthogonal functionalities at their focal points allow them to be conjugated to cargo using simple synthetic methods. (mdpi.com)
  • To reach this goal, we used both biophysical and cell biology methods. (diva-portal.org)
  • Moreover, we describe methods for permeation and cell viability assessment in the Caco-2 cell culture model with and without implementation of biosimilar mucus. (springer.com)
  • The current RNA capture methods involve sorting cells in suspension from acutely dissociated tissue, and thus can lose information about cell morphology and microenvironment. (wikipedia.org)
  • Gene expression is highly tissue specific, therefore with traditional RNA capture methods one must be cautious in the interpretation of gene expression patterns, as they often reflect expression of a heterogeneous mix of cell populations. (wikipedia.org)
  • Åmand HL, Rydberg HA, Fornander LH, Lincoln P, Nordén B, Esbjörner EK (2012) Cell surface binding and uptake of arginine-and lysine-rich penetratin peptides in absence and presence of proteoglycans. (springer.com)
  • This mechanism explains how key ingredients, such as the cooperation among the peptides, the large positive charge, and specifically the guanidinium groups, contribute to the uptake. (wikipedia.org)
  • Quality control of cationic cell-pene. (ugent.be)
  • In tumors, proteases such as MMP-2 and -9 cleave the linkers (green), releasing polyanions (red) and leaving a highly cationic molecule to stick to and enter cells. (nih.gov)
  • The first CPP was discovered independently by two laboratories in 1988, when it was found that the trans-activating transcriptional activator (TAT) from human immunodeficiency virus 1 (HIV-1) could be efficiently taken up from the surrounding media by numerous cell types in culture. (wikipedia.org)
  • Among these three peptides, one peptide (P8), derived from voltage-dependent L-type calcium channel subunit alpha-1D, was able to accumulate inside in a variety of cell types very efficiently through a rapid dose-dependent process. (ovid.com)
  • In this study, the effect on early events (1 h treatment) in transfection by PepFect14 (PF14), with or without oligonucleotide cargo on gene expression, in HeLa cells, have been investigated. (sigmaaldrich.com)
  • These peptides are known to form noncovalent, nano-sized complexes with diverse oligonucleotide cargoes. (diva-portal.org)
  • The general purpose of this thesis is to reveal the mechanisms by which our in house designed peptides enter cells and allow the successful transport of biofunctional oligonucleotide cargo. (diva-portal.org)
  • The widespread application of cell penetrating agents to clinical therapeutics and imaging agents relies on the ability to prepare them on a large scale and to readily conjugate them to their cargos. (mdpi.com)
  • To prevent cell adhesion, we developed genetically engineered polypeptides with the potential to inhibit metastases. (aacrjournals.org)
  • The majority of chemotherapeutic agents used in clinics are highly toxic to both tumor cells and normal tissues due to the lack of specificity. (dovepress.com)
  • 0.01) and resulted in more cell apoptosis as a result of DNA disruption as well as a relatively lower tumor growth ratio (T/C%). Histological examination did not show any signs of necrosis or inflammation in normal tissues, but large cell dissolving areas were found in tumors following the treatment of animals with CPPL(DOX). (dovepress.com)
  • Tumor cell metastasis is a complex, multi-step process that is a major cause of morbidity and death amongst cancer patients. (aacrjournals.org)
  • The "cargo" is associated with the peptides either through chemical linkage via covalent bonds or through non-covalent interactions . (wikipedia.org)
  • Small-angle X-ray scattering (SAXS) measurements reveal a striking difference in intermolecular interactions between two short highly charged peptides - deca-arginine (R10) and deca-lysine (K10). (lu.se)
  • Cell adhesion plays a critical role in the development of metastatic cancer, and it is mediated by interactions between receptors on the cell surface and ligands of the extracellular matrix or other surfaces. (aacrjournals.org)
  • Furthermore, while the TAT-SNX9 peptide prevented TGF-β's profibrotic activity in vitro as well as in 2 murine treatment models of pulmonary fibrosis, a 3-amino acid point mutant that was unable to bind pSMAD3 proved ineffective. (jci.org)
  • More than two decades ago, Frankel and Pabo as well as Green and Loewenstein simultaneously reported the first peptide, which was able to cross the aforementioned barriers. (degruyter.com)
  • In the current study, we have developed a cell-penetrating peptide (CPP) conjugate of the HIV TAT protein that is fused to an aminoterminal sequence of sorting nexin 9 (SNX9), which was previously shown to bind phosphorylated SMAD3 (pSMAD3). (jci.org)
  • Even in the same cell type, tissue measurements, where a population of cells is obtained, mask both low-level mRNA expression in single cells and variation in expression between cells. (wikipedia.org)
  • We report on different cell-penetrating peptides applied for vectorization of splice-correcting oligonucleotides using both covalent conjugation and non-covalent nanoparticle formation approach. (teknoscienze.com)
  • Hilgendorf C, Spahn-Langguth H, Regårdh CG, Lipka E, Amidon GL, Langguth P (2000) Caco-2 versus Caco-2/HT29-MTX co-cultured cell lines: permeabilities via diffusion, inside- and outside-directed carrier-mediated transport. (springer.com)
  • In this study, p21-ELP-Bac and its control, ELP-p21, were used in cell proliferation studies using the pancreatic cancer cell lines Panc-1, MiaPaca-2, and S2013. (dovepress.com)
  • María García-Díaz is acknowledged for supplying the protocols for the mucus preparation and the permeation study using Caco-2 cell monolayers supplemented with biosimilar mucus. (springer.com)
  • In addition, competitive inhibition with heparin revealed the involvement of cell-surface proteoglycans in P8 uptake. (ovid.com)