Many anticancer drugs, such as doxorubicin (DXR), intercalate into nuclear DNA of cancer cells, thereby inhibiting their growth. However, it is not well understood how such drugs interact with mitochondrial DNA (mtDNA). Using cell and molecular studies of cultured cells, we show that DXR and other DNA intercalators, such as ethidium bromide, can rapidly intercalate into mtDNA within living cells, causing aggregation of mtDNA nucleoids and altering the distribution of nucleoid proteins. Remodelled nucleoids excluded DXR and maintained mtDNA synthesis, whereas non-remodelled nucleoids became heavily intercalated with DXR, which inhibited their replication, thus leading to mtDNA depletion. Remodelling was accompanied by extensive mitochondrial elongation or interconnection, and was suppressed in cells lacking mitofusin 1 and optic atrophy 1 (OPA1), the key proteins for mitochondrial fusion. In contrast, remodelling was significantly increased by p53 or ataxia telangiectasia mutated inhibition (ATM),

DNA has a strong affinity for many heterocyclic aromatic dyes, such as acridine and its derivatives. Lerman in 1961 first proposed intercalation as the source of this affinity, and this mode of DNA binding has since attracted considerable research scrutiny. Organic intercalators can inhibit nucleic acid synthesis in vivo, and they are now common anticancer drugs in clinical therapy.. The covalent attachment of organic intercalators to transition metal coordination complexes, yielding metallointercalators, can lead to novel DNA interactions that influence biological activity. Metal complexes with σ-bonded aromatic side arms can act as dual-function complexes: they bind to DNA both by metal coordination and through intercalation of the attached aromatic ligand. These aromatic side arms introduce new modes of DNA binding, involving mutual interactions of functional groups held in close proximity. The biological activity of both cis- and trans-diamine PtII complexes is dramatically enhanced by the ...

Owing to the rise in drug resistance in tuberculosis combined with the global spread of its causative pathogen, Mycobacterium tuberculosis (Mtb), innovative anti mycobacterial agents are urgently needed. Recently, we developed a novel primase-pyrophosphatase assay and used it to discover inhibitors of an essential Mtb enzyme, primase DnaG (Mtb DnaG), a promising and unexplored potential target for novel antituberculosis chemotherapeutics. Doxorubicin, an anthracycline antibiotic used as an anticancer drug, was found to be a potent inhibitor of Mtb DnaG. In this study, we investigated both inhibition of Mtb DnaG and the inhibitory activity against in vitro growth of Mtb and M. smegmatis (Msm) by other anthracyclines, daunorubicin and idarubicin, as well as by less cytotoxic DNA intercalators: aloe-emodin, rhein and a mitoxantrone derivative. Generally, low-μM inhibition of Mtb DnaG by the anthracyclines was correlated with their low-μM minimum inhibitory concentrations. Aloe-emodin displayed threefold

There are several ways molecules (in this case, also known as ligands) can interact with DNA. Ligands may interact with DNA by covalently binding, electrostatically binding, or intercalating.[1] Intercalation occurs when ligands of an appropriate size and chemical nature fit themselves in between base pairs of DNA. These ligands are mostly polycyclic, aromatic, and planar, and therefore often make good nucleic acid stains. Intensively studied DNA intercalators include berberine, ethidium bromide, proflavine, daunomycin, doxorubicin, and thalidomide. DNA intercalators are used in chemotherapeutic treatment to inhibit DNA replication in rapidly growing cancer cells. Examples include doxorubicin (adriamycin) and daunorubicin (both of which are used in treatment of Hodgkins lymphoma), and dactinomycin (used in Wilms tumour, Ewings Sarcoma, rhabdomyosarcoma). Metallointercalators are complexes of a metal cation with polycyclic aromatic ligands. The most commonly used metal ion is ruthenium(II), ...

Kazuo Nakamoto pioneered the use of metal isotopes to elucidate the involvement of metals in low-frequency vibrations in metallic complexes and was among the first to use matrix isolation techniques to prepare and characterize unstable specie. He is the author of Infrared and Raman Spectra of Inorganic and Coordination compounds, Fifth Edition (Wiley). Masamichi Tsuboi studies DNA and RNA structures, drug-DNA interaction, protein conformation, protein-nucleic acid recognition, and virus structure using a variety of physicochemical and biomedical techniques including X-ray diffraction, UV-Visible, IR/Raman , and NMR spectroscopy.. Gary D. Strahan uses physico-chemical techniques to understand biological systems relevant to pharmaceutical discovery and agricultural and natural product analyses. His work has emphasized spectroscopic methods, NMR, and computational modeling to determine the structures and properties of multistranded DNA, drug-DNA complexes, carbohydrates, and other biomolecules, as ...

The last few years have witnessed the creation of new generations of sequence reading compounds, which have incredible potential for targeting specific DNA sequences. In Drug-DNA Interaction Protocols

Platinum(ii)-based DNA intercalators where the intercalating ligand is 1,10-phenanthroline or a phenanthroline derivative and where the ancillary ligand is either achiral (e.g. ethylenediamine) or chiral (e.g. diaminocyclohexane) show a range of cytotoxicities with a defined structure-activity relationship. Dalton Discussion 10: Applications of metals in medicine and healthcare RACI100: Celebrating Australian Chemistry

Methods and kits for the quantitation of cellular DNA and cell numbers are provided. Passive element uptake, element-labeled DNA intercalators, and element labeled affinity reagents are used to quantify DNA and cells. The DNA and the cells are analyzed by elemental analysis, including ICP-MS. The methods and kits provide a fast and accurate analysis of cellular DNA and cell numbers.

yesterday, asked Stephane to order BD Biocoat plastic including some large 150 cm2 tissue culture flasks; these to grow up lots of cells for cornal implant idea weve developed. For live cell labeling, have ordered Molecular Probes CellTracker for initial implants (membrane dye, will dilute after 4 cell divisions or so) (but see this article, PDF for Vybrant DyeCycle which does the same but in the nucleus; I was ill at ease using a DNA intercalator), and have also ordered an anti-Ki-67 epitope, which appears on cells undergoing proliferation (absent from G0 stage) and is reportedly human-specific, though Id have to look up those references again ...

Introduction to Genetic Analysis 8th Edition, Anthony J.F. Griffiths, Susan R. Wessler, Richard C. Lewontin, William M. Gelbart, David T. Suzuki, Jeffrey H. Miller ...

Intercalation. The preparation of oxide and sulphide compounds whose structures are capable of incorporating organic and organometallic compounds between structural layers has led to an explosion of research into intercalation chemistry in recent years. A variety of techniques are used to facilitate this. Whilst some intercalation reactions occur extremely rapidly and without activation, others require the use of thermal or ultrasonic techniques, or even mechanical shaking. Unfortunately, these methods may lead to an undesirable degradation of the products crystalline structure, leading to difficulties in its characterisation. Once again, this represents a poorly researched area despite the promising findings of initial studies.. The intercalation of pyridine and pyridine derivatives into the layered compound a-VO(PO4) proceeds slowly under thermal conditions. The products may be formed with a maximum stoichiometry of a-VO(PO4).py0.85 by exposing the host to the pure pyridine derivative, or ...

Targeted delivery of chemotherapeutic agents is normally a fresh approach for the treating cancer, which gives elevated selectivity and reduced systemic toxicity. rat liver organ lysosomal homogenate, that was in a position to bind to DNA an oxime connection to some GnRH-III derivative where Ser constantly in place 4 was changed by Lys(Ac) [13]. Daunorubicin (Amount 1A) is really a chemotherapeutic agent 1369761-01-2 supplier which inhibits Mouse monoclonal to FOXD3 the cell proliferation and department by mechanisms such as for example DNA intercalation, inhibition of topoisomerase II, free of charge radical development, lipid peroxidation, etc. Despite its scientific benefits, the administration of free of charge Dau is accompanied by toxic unwanted effects, the most serious one getting cardiotoxicity [14], [15]. As a result, the connection of Dau to GnRH-based concentrating on moieties should offer elevated selectivity and reduced systemic toxicity [12]. Weve recently shown which the ...

TY - JOUR. T1 - Screening of Threading Bis-Intercalators Binding to Duplex DNA by Electrospray Ionization Tandem Mass Spectrometry. AU - Mazzitelli, Carolyn L.. AU - Chu, Yongjun. AU - Reczek, Joseph J.. AU - Iverson, Brent L.. AU - Brodbelt, Jennifer S.. PY - 2007/2/1. Y1 - 2007/2/1. N2 - The DNA binding of novel threading bis-intercalators V1, trans-D1, and cis-C1, which contain two naphthalene diimide (NDI) intercalation units connected by a scaffold, was evaluated using electrospray ionization mass spectrometry (ESI-MS) and DNAse footprinting techniques. ESI-MS experiments confirmed that V1, the ligand containing the -Gly3-Lys- peptide scaffold, binds to a DNA duplex containing the 5′-GGTACC-3′ specific binding site identified in previous NMR-based studies. The ligand formed complexes with a ligand/DNA binding stoichiometry of 1:1, even when there was excess ligand in solution. Trans-D1 and cis-C1 are new ligands containing a rigid spiro-tricyclic scaffold in the trans- and cis- ...

Bifunctional molecules having a DNA intercalator or DNA groove binder linked to ethylene diamine tetraacetic acid such as compounds having the formula: ##STR1## wherein R is methyl or ethyl. Also, the method of cleaving DNA by contact with one of the above-identified molecules in the presence of ferrous ion and oxygen. The process of preparing said molecules by the reaction of P-carboxy methidium halide, p-carboxy ethidium halide, or other DNA intercalator or DNA groove binder with 1-3-diaminopropane followed by condensation with ethylenediamine tetraacetic acid. Distamycin-EDTA.Fe(II)(DE.FE(II)) contains EDTA attached to the amino terminus of the groove binder tripeptide (tris-N-methylpyrrolecarboxamide). De.Fe(II) cleaves DNA contiguous to a five base pair A+T rich sequence. This is a novel and unique molecule and superior in sequence specificity to the naturally occurring antitumor compound used in man, bleomycin which cleaves DNA at a two base pair recognition site. EDTA-distamycin

TY - JOUR. T1 - Molecular and cellular toxicological profiling of DNA bis-intercalator, quinoxaline compounds. T2 - echinomycin as the versatile lead. AU - Park, Yoon Sun. AU - Shin, Woon Seob. AU - Kim, Cheol Su. AU - Ahn, Chan Mug. AU - Qi, Xu Feng. AU - Kim, Soo-Ki. PY - 2018/1/1. Y1 - 2018/1/1. N2 - Of quinoxaline compounds, echinomycin is classically known as an antitumor agent which binds to DNA via a mechanism of bis-intercalation. In addition to intercalation, quinoxaline compounds such as echinomycin, echinomycin derivatives or analogues might control anomalous cellular proliferation in eukaryotes via specifically triggering cellular signaling pathways in mitochondria, as well as under hypoxia. Further, since echinomycin was proven to be a specific inhibitor of HIF-1α, these novel mechanisms could be clinically applied in the development of therapeutics against cancer, infection, obesity, fibrosis, and autoimmune disease. Herein, this review focuses on the current toxicological ...

Amikhelline is an antimitotic drug. It acts as a DNA intercalator and inhibits DNA polymerase. Turchini MF, Geneix A, Perissel B, Malet P, Turchini JP. Characterization of chromosomal aberrations induced in man by various antimitotic agents. (French). Comptes Rendus des Seances de la Societe de Biologie et de ses Filiales. 1985;179(3):331-9. PMID 2417673 Rucheton M, Jeanteur P. Studies on amikhellin. I. Intercalative binding to double-stranded DNA. Biochimie. 1973;55(11):1415-20. PMID 4364376 Rucheton M, Jeanteur P. Studies on amikhellin. II.-Inhibition of dna-polymerase from murine sarcoma leukemia virus. Biochimie. 1976;58(6):689-95. PMID ...

Drugs that inhibit the action of topoisomerase enzymes (regulatory enzymes that catalyze the breakage and religation of DNA) are an important class of anticancer drugs. The drugs bind reversibly to form ternary drug/DNA/enzyme complexes that result in cytotoxic DNA breaks, primarily by preventing the relegation step. The drugs are usually classified by their spectrum of inhibition, as inhibitors of topo I, topo II, or of both enzymes (dual topo I/II inhibitors). The majority of the topo II and dual topo I/II inhibitors are DNA intercalators, where a flat polyaromatic drug chromophore intercalates between the base pairs, driven primarily by stacking and electrostatic interactions. There is also a substantial and diverse class of drugs with little direct DNA affinity but which nevertheless form ternary complexes. Inhibitors of topo I are primarily of the latter type, most being analogues of the natural product camptothecin. The major deficiencies of this class are the instability of the essential ...

Small transition metal molecules have been the object of many studies due to their interactions with DNA and the resulting effects on the regulation of DNA transcription and replication, as well as their potential as pharmaceuticals. Ru(II) compounds are especially useful as probes due to their stability and photophysical properties. Bis(bipyridyl) Ru(II) complexes of pteridinyl-phenanthroline ligands have been of particular interest because pteridinyl ligands possess H-bonding patterns complementary to the purine and pyrimidine bases of DNA and RNA. The pteridinyl ligand of these Ru-pteridine complexes is capable of inserting itself between the base pairs of DNA, thus binding to DNA via intercalation. Other metal complexes, including certain Co(III) complexes, have been known to cleave DNA in the presence of light (photoactivated cleavage of DNA). Such metallointercalators are practical for their high affinity for double-stranded DNA and because they include a range of redox-active metal centers and

The synthesis of a new bifunctional compound in which two aminoacridine chromophores are linked by the bicyclic depsipeptidic backbone of des-N-tetramethylTriostin A is described. The molecule, bis-[(9-acridinyl)-D-seryl-L-alanyl-L-cysteinyl-L-valine] dilactone disulphide, structurally analogous to the antibiotic anti-tumour drug Triostin A, is shown to possess a high affinity to DNA and to act as a bis-intercalator on the basis of spectroscopic, viscosimetric and thermal-denaturation studies. This model constitutes the first attempt of a synergic association between a peptidic moiety that mimics a naturally occurring drug and aminoacridine, the two parts themselves each exhibiting a high affinity for the DNA target. ...

LMP744 hydrochloride (MJ-III65 hydrochloride) is a DNA intercalator and Topoisomerase I (Top1) inhibitor with antitumor activity. - Mechanism of Action & Protocol.

Metalloinsertion represents a general binding mode for the binding of bulky metal complexes to destabilized mismatches. With intercalative binding, well-matched, hydrogen-bonded base pairs separate, increasing the helical pitch, so that an aromatic heterocyclic ligand can stack within the DNA duplex, essentially like another base pair [11]. For metalloinsertion, the flat aromatic heterocyclic ligand is simply too large to insert easily into the DNA duplex and instead, to accommodate the inserting ligand, the base pairs must separate and be ejected from the helix [12,13]. This ejection only occurs easily at destabilized mismatched sites, and thus the binding affinity for mismatches correlates with the thermodynamic instability of the mismatch, the ease of separation and ejection. Several crystal structures have shown that metalloinsertion occurs from the minor groove side with no increase in helical pitch [12,13,14]. As a result, for the tris(chelate) metalloinsertors, binding within the small ...

Research is the foundation to scholarship. Research in my lab is primarily focused on the application of chemistry to solving problems related to biomolecular structure, function, and activity, especially as it relates to drug design and discovery. More precisely, we apply chemical synthesis, biological screening, and structural biology to understand the basis to molecular recognition and the physical forces that drive function.. For example, our work on opioid recognition defined the first structural models by which highly selective agonists and antagonists could be rationally designed. In the field of cancer and topoisomerase function, we designed characterized DNA binding agents that selectively inhibited topoisomerase II by threading DNA duplex and quadraplex structures thereby blocking strand cleavage. These catalytic inhibitors were further shown to avoid formation of linear DNA fragments following treatment reducing the toxic effects commonly associated with topoisomerase poisons. Using ...

Video articles in JoVE about alkylating agents include Assessment of Endothelial Cell Migration After Exposure to Toxic Chemicals, Application of Laser Micro-irradiation for Examination of Single and Double Strand Break Repair in Mammalian Cells, In Vitro Bioluminescence Assay to Characterize Circadian Rhythm in Mammary Epithelial Cells, CometChip: A High-throughput 96-Well Platform for Measuring DNA Damage in Microarrayed Human Cells, Busulfan as a Myelosuppressive Agent for Generating Stable High-level Bone Marrow Chimerism in Mice, Percutaneous Hepatic Perfusion (PHP) with Melphalan as a Treatment for Unresectable Metastases Confined to the Liver, Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms, Transposon Mediated Integration of Plasmid DNA into the Subventricular Zone of Neonatal Mice to Generate Novel Models of Glioblastoma, Genome-wide Mapping of Drug-DNA Interactions in Cells with COSMIC

Cel organisatie van craniofaciale botten is al lang de hypothese, maar niet direct zichtbaar. Multispectrale cell labeling en in vivo levende ...

Linear and circular dichroic spectroscopies have been employed to investigate the effects of small DNA ligands on the interactions of two proteins which bind to the minor groove of DNA, viz. RecA protein from Escherichia coli and deoxyribonuclease I (bovine pancreas). Ligands representing three specific non-covalent binding modes were investigated: 4,6-diamidino-2-phenylindole and distamycin A (minor groove binders), methyl green (major groove binder), and methylene blue, ethidium bromide and ethidium dimer (intercalators). Linear dichroism was demonstrated to be an excellent detector, in real time, of DNA double-strand cleavage by deoxyribonuclease I. Ligands bound in all three modes interfered with the deoxyribonuclease I digestion of dsDNA, although the level of interference varied in a manner which could be related to the ligand binding site, the ligand charge appearing to be less important. In particular, the retardation of deoxyribonuclease I cleavage by the major groove binder methyl green

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality, such that it the second most frequent cause of cancer death worldwide. Due to its heterogeneous composition and aggressive behavior, it is resistant to conventional therapies and also Sorafenib and Regorafenib which are FDA-approved multikinase inhibitors targeting pathways involved in angiogenesis and proliferation. The mechanisms behind the acquired resistance to Sorafenib were described as activation of compensatory pathways such as PI3K/Akt/mTOR, JAK-STAT, epithelial to mesenchymal transition (EMT), microenvironment and presence of cancer stem cells. Liver cancer stem cells originate from damaged and transformed hepatic progenitor cells (HPCs) which are found responsible for chemo-resistance, tumor relapse, and metastasis. For this reason, the effects of PI3K/Akt/mTOR inhibitors, Sorafenib and DNA intercalators on the enrichment of LCSCs were investigated. CD133+/EpCAM+ population from HCC cells were ...

Polyammoniumcations have been used as DNA targeting ligands for a variety of DNA active reagents, for example radioprotectors and anti-tumour antibiotics, which do not rely on sequence specific binding for their activity. It is proposed that these ligands have a high affinity for DNA but exhibit an external (or loose) electrostatic binding interaction which enables them to remain mobile along DNA without dissociation of the drug: DNA complex. Polyammoniumcations based on the polytetraalkylammonium and polyprotonated ammonium salts of the naturally occurring polyamines spermine and spermidine were prepared. The synthesis of drug-ligand conjugates requires either selective mono-protection or mono-derivatisation of polyamines. These syntheses are problematic because of the combination of primary and secondary amine centres encountered and difficulties in handling the polyamines. Two strategies for achieving selective derivatisation were explored: the total synthesis of protected polyamines and ...

AMETEK Brookfield, the world standard for viscosity measurement and control, is offerings its Practical Course on Viscosity Measurements. This popular course was created to help AMETEK Brookfield Vi

See moreThe synthesis and characterisation of a new dinuclear GdIII-PtII complex (1·PF6) containing a functionalised macrocyclic 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid derivative linked to a PtII-terpy (terpy = 2,2′ : 6′,2″-terpyridine) unit by means of a short thiolato linker are reported. The complex was synthesised in six steps from cyclen by means of a modular synthetic strategy. A preliminary DNA-binding study with calf-thymus DNA (ct-DNA) was performed on 1·PF6 by means of linear dichroism (LD). The observed changes in the DNA LD signal in the presence of the metal complex are fully consistent with an intercalative binding mode. Furthermore, an induced negative LD signal in the ultraviolet absorption region of the complex provides strong evidence of a strong DNA-binding interaction. The in vitro cytotoxicity of 1·PF6 towards a human glioblastoma cell line (T98G) was also determined ...

Doxorubicin is routinely used in combination with cisplatin for the treatment of ovarian cancer (11), and although initially successful, therapy often ultimately fails because of acquired resistance to one or both of these agents. A series of compounds with both DNA intercalation and cross-linking potential was investigated against the A2780 human ovarian cancer cell line, the MDR1 overexpressing variant (2780AD), and the 2780/cp70 cell line, which is defective in the hMLH1 subunit with consequent loss of DNA mismatch repair activity. The results from the cytotoxicity investigation highlighted mechanisms of resistance that distinguished the chloroethylaminoanthraquinones from the noncovalent binding hydroxyethylaminoanthraquinones. All of the compounds tested, with the exception of ZP289M, were found to be of the same order of potency as doxorubicin in the A2780 cell line, but showed a wide-ranging variation in the extent of cross-resistance in the doxorubicin-resistant cell line 2780AD (Table ...

In addition, in-service oil analysis includes various other parameters that have to be tested. Anton Paar provides the SVM 4001 and SVM 3001 Viscometers for measurements according to to ASTM D7042 respectively to DIN 51659-2 ASTM D7042. It is an excellent alternative to conventional capillary viscometers for fast and economical measurement of the low-shear kinematic viscosity over a wide temperature range. Consequently, ASTM D2270 references ASTM D7042 for the determination of kinematic viscosity. Automation of viscosity measurements provides several benefits over conventional manual measurements due to reduced handling errors, higher reproducibility, reduced costs per sample and increased productivity in the laboratory. This report describes specifically how to test inservice lube oils with the SVM 4001 in combination with Xsample 530 and a manually filled SVM 3001 to get data comparable to ASTM D445. ...

Brookfield, a world standard for viscosity measurement and control, offers two hands-on courses that equip users of Brookfield instruments with the knowledge to get the most out of their viscosity test methods. These one-day training sessions are presented in easy-to-understand terms that give attendees the working know-how to verify and improve upon the data required for meaningful R&D and successful QC testing.

Chelmsford, MA -- A new ASTM Standard Test Method supports the simple, convenient, and accurate viscosity measurement method employed in portable MiniVisc ...

Poulten Selfe and Lee Ltd is a UK company specializing in the viscosity measurement of new and used oils. The company was incorporated in 1931 and manufactures an established range of...

First, the effects of intervening mismatches on DNA structure, dynamics and DNA charge transport reactivity is examined. The pi?stacked DNA base pairs mediate charge transport chemistry over long molecular distances in a reaction that is exquisitely sensitive to DNA sequence dependent conformation and dynamics. To examine the long-range charge transport as a function of intervening base mismatches, a series of DNA oligonucleotides were synthesized that incorporate a ruthenium intercalator, [Ru(phen)(bpy?)(dppz)]2+ (phen = 1,10 phenanthroline; bpy = 4-butyric acid-4-methylbipyridine; dppz = dipyrido[3,2-a:2,3-c]phenazine) linked covalently to the 5 terminus of one strand and containing two 5-GG-3 sites in the complementary strand. Single base mismatches were introduced between the two guanine doublet steps, and the efficiency of transport through the mismatches was determined through measurements of the ratio of oxidative damage at the guanine doublets distal versus proximal to the ...

Product Review: The Babyzen Yoyo2 travel system pushchair is an update on the Yoyo+ which was itself an update on the original Yoyo. On first launching, it took the travelling-pushchair world by storm thanks to its lightweight ...

10-Bromonaphth[2,3-c]acridine-5,8,14(13H)-trione/ACM52636596 can be provided in Alfa Chemistry. We are dedicated to provide our customers the best products and services.

Vosaroxin is a first-in-class, small molecule quinolone derivative belonging to the compound class of naphthyridines that was discovered by Dainippon

1H- and 31P-n.m.r. spectroscopy were used to characterize the solution structure of the 1:1 complex formed between the antitumour… Expand ...

At first glance, the TOTO Neorest 550H and the TOTO Neorest AC look like they have nothing in common. Under the surface, however, theyre much more similar than they look, with only a few differences

DNA minor groove binders (MGBs) are known to influence gene expression and are therefore widely studied to explore their therapeutic potential. We identified shape-based virtual screening with ROCS as a highly effective computational approach to enrich known MGBs in top-ranked molecules. Discovery of ten previously unknown MGBs by shape-based screening further confirmed the relevance of ligand shape for minor groove affinity. Based on experimental testing we propose three simple rules (at least two positive charges, four nitrogen atoms, and one aromatic ring) as filters to reach even better enrichment of true positives in ROCS hit lists. Interestingly, shape-based ranking of MGBs versus FDA-approved drugs again leads to high enrichment rates, indicating complementary coverage of chemical shape space and indicating minor groove affinity to be unfavorable for approval of drugs targeting proteins ...

Previously reported structure−activity relationships have shown two features for effective antitumor activity of titanium β-diketone complexes: (a) ligand asymmetry and (b) the presence of planar substitutents on the ligand. Mono- and dinuclear derivatives, studied with diffraction and DFT methods show that (a) is consistent with different Ti−O(β-diketonato) bond lengths, which are longer than Ti−O(oxo) and Ti−O(alkoxy) ones. π−π features observed in dinuclear derivatives correlate with strong reactivity of related complexes with DNA and support DNA intercalation by such planar groups, in agreement with (b). Large variation for Ti−O bond lengths and Ti−O−C bond angles in the ethoxy moiety is associated with the titanium withdrawing effect and oxygen bonding s character; it is confirmed through exploration of the Cambridge crystallographic database. This ethoxy geometrical flexibility also suggests versatile accommodation in protein pockets and/or other biological targets. ...

TY - GEN. T1 - A method of numerical viscosity measurement for solid-liquid mixture. AU - Nomura, Reika. AU - Terada, Kenjiro. AU - Takase, Shinsuke. AU - Moriguchi, Shuji. PY - 2018/1/1. Y1 - 2018/1/1. N2 - We present a space-time homogenization procedure for multiscale modeling of solid-liquid mixture. The derived mathematical model enables us to set up two separate governing equations at both macro- and micro-scales. The fluid in the macroscopic governing equation is teated as an equivalent homogeneous medium with average or homogenized viscosity and is regarded as an incompressible Newtonian fluid, whose motion is assumed to be governed by the Navier-Stokes equations. The microscopic equations of motion governing the coupling phenomenon of the fluid and solid particles in a certain local domain and are solved to determine the microscopic flow fields under adequate boundary and loading conditions. Then the macrosopic viscosity is determined as the quantity averaged over the microscopic domain ...

Following the launch of the new m-VROCi, Viscometer/Rheometer On a Chip, at Pittcon 2014, Malvern Instruments will focus on the unique technology of this system and the considerable benefits it delivers in a webinar on 16 April 2014. The m-VROCi provides safe, accurate viscosity measurement for low viscosity industrial fluids, under conditions that reflect those that apply during end-product use.

pH and Viscosity Measurement tutorial of Industrial Instrumentation course by Prof Alok Barua of IIT Kharagpur. You can download the course for FREE !

Lucideon provides rheological characterisation & viscosity measurements across the full range of shear rates encountered in production, from pouring or gentle mixing through to spraying & spinning

The commonly used fluorescent dye YOYO-1 (YOYO) has, using bulk techniques, been demonstrated to stain DNA heterogeneously at substoichiometric concentrations. We here, using nanofluidic channels and fluorescence microscopy, investigate the heterogeneous staining on the single DNA molecule level and demonstrate that the dye distribution is continuous. The equilibration of YOYO on DNA is extremely slow but can be accelerated by increasing the ionic strength and/or the temperature. Furthermore, we demonstrate how to use the heterogeneous staining as a tool for detailed and time-efficient studies of how fluorescent dyes affect the physical properties of DNA. We show that the relative increase in extension of DNA with increasing amount of YOYO bound is higher at low ionic strengths and also extrapolate the extension of native DNA. Our study reveals important information on how YOYO affects the physical properties of DNA, but it also has broader applications. First, it reveals how cationic intercalators,

Cambridge Viscosity is the global leader in fluid viscosity measurement, including oil and gas; petroleum and biofuels; coatings, paints, and inks; pharmaceuticals, and other substances. Where accurate viscosity measurement is mission critical in both process and laboratory environments, Cambridge Viscosity technologies are chosen time and time again.. Our leadership is based on a quarter-century of experience, the extraordinary range of our products - including both in-line and in-tank applications - and our innovative proprietary technology. Our customers include leading organisations in oil and gas exploration, refining, automotive, research, industrial materials, and other high-stakes fields.. Cambridge Viscosity has set the standard for extraordinarily precise, reliable, and virtually maintenance-free viscosity measurement systems. Our sensors and viscometer systems conform to ASTM, DIN, JIS and ISO standards, with a range of models designed to meet specific industry and application needs. ...

Since the properties of small molecules can change upon conjugation to proteins, we investigated the binding of CB[8] to TMV-6 following the confirmation of the TMV-6 conjugate. Since the solutions of TMV-6 at concentrations required for ITC characterization were subject to viscosity and adhesion issues, a fluorescence titration was used instead to determine a dissociation constant. In this case, neither TMV-6 nor CB[8] contain fluorophores, so a competitive binding strategy incorporating a fluorophore was implemented. Acridine-3,6-diamine, or proflavin (PF), is an acridine derivative that is fluorescent as a free molecule in aqueous solutions, but its fluorescence becomes quenched68,69 upon binding inside the cavity of CB[8]. A fluorescence titration of increasing concentrations of TMV-6 (0-20 μM relative to TEMPO) titrated into solutions with a constant concentration of the CB[8]⊃PF (0.2 μM) complex was performed. Upon the addition of increasing concentrations of TMV-6, the observed ...

Sigma-Aldrich offers Aldrich-A38401, 9-Aminoacridine hydrochloride monohydrate for your research needs. Find product specific information including CAS, MSDS, protocols and references.

On a more intentional basis, biotechnological tools such as zinc finger nucleases, TALENs, and the (oh-so-sexy) CRISPR system can be used to specifically alter genome sequences of choice. ZFNs are in particular being used as a gene therapy tool for just that reason.. Otherwise, viruses (and transposons) that insert into the genome can cause specific mutations or errors if they do so non-randomly. Figuring that out, though, can be tricky; most oncoviruses cause mutations through specific genes that allow uncontrolled growth and tumorigenesis, not in a site-directed manner. There is, however, a growing hypothesis that certain retroviruses which tend not to cause cancer, in particular HIV, may be inserting into sites with certain characterizations, such as chromatin level. That is far from known, though.. If youre looking for random causes, thats easy. Anything that disrupts DNA repair mechanisms such as p53 or Rb will do that. For chemicals, intercalators such as ethidium bromide and thalidomide ...

TY - JOUR. T1 - Viscosity change and structural transition of Molten Fe at 5 GPa. AU - Terasaki, Hidenori. AU - Kato, Takumi. AU - Urakawa, S.. AU - Funakoshi, K.. AU - Sato, K.. AU - Suzuki, A.. AU - Okada, T.. PY - 2002/4/15. Y1 - 2002/4/15. N2 - The in situ viscosity measurements of the pure molten Fe under high pressures were made by falling sphere X-ray radiography method. Viscosity coefficients at about 2000 K were 15-24 mPa s at 2.7-5.0 GPa, and 4-9 mPa s at 5.0-7.0 GPa. Drastic decrease was found at around 5 GPa, at which stable solid phase below the melting temperatures change from delta (bcc) to gamma (fcc) phases. The observation indicates the possibility that the structural change in the molten Fe occurs in a narrow pressure interval (1 GPa) at the similar condition with the phase transformation in the solid.. AB - The in situ viscosity measurements of the pure molten Fe under high pressures were made by falling sphere X-ray radiography method. Viscosity coefficients at about 2000 K ...

Mechanistic Insight into Catalyst-Transfer Polymerization of Unusual Anion-Radical Naphthalene Diimide Monomers: An Observation of Ni(0) Intermediates

Paolo Canuti, Arrigo Gregnanin, Enzo Michele Piccirillo, Mario Sagri, Paolo Tacconi; Volcanic intercalation in the Mesozoic sediments of the Kulubi area (Harrar, Ethiopia). Italian Journal of Geosciences ; 91 (4): 603-614. doi: Download citation file:. ...

This is an important measurement for a wide range of products that is currently time consuming and expensive. The new device will be small enough so that in future the whole measurement will be able to be made in a small hand held device, possibly looking rather like a smart hypodermic needle. The small size brings several advantages including increased speed, reduced cost and environmental impact since fewer resources are used in manufacture and use. ...

Following the launch of the new m-VROCi, Viscometer/Rheometer On a Chip, at Pittcon 2014, Malvern Instruments will focus on the unique technology of this system and the considerable benefits it delivers in a webinar on 16 April 2014. The m-VROCi prov

BABYZEN Parasol in Taupe protects your little one from harmful UV rays. It has been designed to easily clip onto the YOYO² strollers, the lightweight design offers UPF50+ protection and is easy to collapse, detach and store away when not in use.Features: Reinforced rib seams Showerproof polyester Offers UPF50+ protecti

Get ready for high flying action with the HI YOYO. Sturdy 18mm TS shaft and a classic performance rubber grip make any move possible! Get ready for take off!

BondEX Ethidium Bromide Detoxification Cartridges safely remove ethidium bromide as well as SYBR Green from electrophoresis buffers or other aqueous solutions.Easy-to-use, gravity-flow cartridges

BondEX Ethidium Bromide Detoxification Cartridges safely remove ethidium bromide as well as SYBR Green from electrophoresis buffers or other aqueous solutions.Easy-to-use, gravity-flow cartridges