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Hepatitis C virus (HCV) poses a major health threat to the world. The recent development of direct-acting antivirals (DAAs) against HCV has markedly improved the response rate of HCV and reduced the side effects in comparison to the interferon-based therapy. Despite this therapeutic advance, there is still a need to develop new inhibitors that target different stages of the HCV life cycle because of various limitations of the current regimens. In this study, we performed a quantitative high throughput screening of the Molecular Libraries Small Molecule Repository (MLSMR) of ∼350,000 chemicals for novel HCV inhibitors using our previously developed cell-based HCV infection assay. Following confirmation and structural clustering analysis, we narrowed down to 158 compounds from the initial ∼3000 molecules that showed inhibitory activity for further structural and functional analyses. We were able to assign the majority of these compounds to specific stage(s) in the HCV life cycle. Three of them ...

This focus review documents the developments in polymer synthesis that involve multicomponent reactions (MCRs) and related sequential reaction systems. Postpolymerization modification and step-growth polymerization reactions based on MCRs and sequential reactions such as the Kabachnik-Fields three-component reaction (KF-3CR) are described. Welcoming more participants in a polymer synthesis; recent years, multicomponent reactions (MCRs) have been gradually integrated into synthetic polymer chemistry, which led to a new synthetic toolbox for a range of interdisciplinary applications. In this focus review, this new trend in polymer chemistry has been summarized with including contributions from the author.

This paper reports the synthesis and screening of a combinatorial peptide library for new affinity ligands for glycosylated haemoglobin (HbA(1c)), which is an important indicator of diabetes control. The new ligands are suitable for large-scale synthesis and overcome the disadvantages of antibodies (unstable and expensive to produce etc.), while remaining as efficient as antibodies in binding to the analyte. The library consisted of 262 144 hexapeptides synthesised using the one-bead-one-compound technique. The hexapeptides attached onto beads were screened with glycosylated haemoglobin HbA(1c). The structures of the peptides exhibiting high affinity were characterised by Edman microsequencing. Computer modelling simulation of one of the lead sequences has shown that this class of ligand has a high affinity and specificity for glycosylated haemoglobin. (C) 1998 Elsevier Science S.A. All rights reserved.. ...

Science Citation Index ExpandedTM, Journal Citation Reports/Science Edition, InCites, Current Contents® - Life Sciences, Chemistry Citation Index®, Reaction Citation Index®, Biological Abstracts, BIOSIS, BIOSIS Previews, MEDLINE/PubMed/Index Medicus, Scopus, EMBASE/Excerpta Medica, Chemical Abstracts Service/SciFinder, ProQuest, ChemWeb, Google Scholar, BIOBASE, EMBiology, Genamics JournalSeek, Cabells Directory, MediaFinder®-Standard Periodical Directory, PubsHub, Index Copernicus, J-Gate, CNKI Scholar, Suweco CZ, TOC Premier, EBSCO, British Library, Ulrichs Periodicals Directory and JournalTOCs.. ...

Science Citation Index ExpandedTM, Journal Citation Reports/Science Edition, InCites, Current Contents® - Life Sciences, Chemistry Citation Index®, Reaction Citation Index®, Biological Abstracts, BIOSIS, BIOSIS Previews, MEDLINE/PubMed/Index Medicus, Scopus, EMBASE/Excerpta Medica, Chemical Abstracts Service/SciFinder, ProQuest, ChemWeb, Google Scholar, BIOBASE, EMBiology, Genamics JournalSeek, Cabells Directory, MediaFinder®-Standard Periodical Directory, PubsHub, Index Copernicus, J-Gate, CNKI Scholar, Suweco CZ, TOC Premier, EBSCO, British Library, Ulrichs Periodicals Directory and JournalTOCs.. ...

TY - JOUR. T1 - Parallel synthesis of N-biaryl quinolone carboxylic acids as selective M1 positive allosteric modulators. AU - Yang, Feng V.. AU - Shipe, William D.. AU - Bunda, Jaime L.. AU - Nolt, M. Brad. AU - Wisnoski, David D.. AU - Zhao, Zhijian. AU - Barrow, James C.. AU - Ray, William J.. AU - Ma, Lei. AU - Wittmann, Marion. AU - Seager, Matthew A.. AU - Koeplinger, Kenneth A.. AU - Hartman, George D.. AU - Lindsley, Craig W.. PY - 2010/1/15. Y1 - 2010/1/15. N2 - An iterative analog library synthesis approach was employed in the exploration of a quinolone carboxylic acid series of selective M1 positive allosteric modulators, and strategies for improving potency and plasma free fraction were identified.. AB - An iterative analog library synthesis approach was employed in the exploration of a quinolone carboxylic acid series of selective M1 positive allosteric modulators, and strategies for improving potency and plasma free fraction were identified.. KW - M. KW - Positive allosteric ...

Streamline the management of your screening compounds with our Aldrich Market Select online order center for small molecule libraries, comprising over 14 million chemistry building blocks and other useful services.

Two different methods are available for synthesizing random peptide libraries. The first technique is known as Split and Mix method which consists of three basic steps: splitting, coupling and mixing. Firstly, resin beads are split in a number of aliquots that equals the number of building blocks to be utilized in the synthesis (splitting). Then, to each resin aliquot one building block is coupled and the reactions are driven to completion (coupling). Following this step, beads are randomly and thoroughly mixed (mixing) and then re-splitted in the same number of aliquots, achieving a set of homogeneous and equimolar collections of compounds. Repetitive execution of these basic steps for n times will thus produce a rapid increase of newly generated molecules, while bead number remains constant. Resin beads encounter one reactant at a time, no more than one compound per bead can be generated (one-bead one-compound-OBOC-library). As reactions are driven to completion, all peptides are generated ...

International trade is stepping into the age of digitally enabled trade, driven by cross-border data flows and interoperability. Concerns for cybersecurity, privacy, and digital sovereignty have prompted the widespread implementation of trade policies regulating cross-border data flows. At present, there is a deficit of information characterizing such policies and analyzing their role in the global economy. We address this deficit through a quantitative analysis of trade in services that seeks both to categorize data-related trade policies and to evaluate the extent to which they are similar to other restrictive measures. We propose a mixture-based clustering pipeline to group trade restrictiveness data and a method for quantifying the difference between the cross-border data flow regulations and other traditional regulations. Our analysis reveals that a significant localization effect among data flow restrictions and that, while highly restrictive data flow policies generally do not overlap with other

As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. ...

Perspectives, compilations, and reviews of modern drug discovery methods:. Bunin, B. A.; Bajorath, J.; Morales, G.; Siesel, B. Cheminformatics: Theory, Practice, and Products 2006, Springer-Verlag, manuscript in press, A summary of the theory and features of the available modern cheminformatics tools.. Bunin, B. A. Increasing the Efficiency of Small Molecule Drug Discovery (In response to an interview with Chris Lipinski on current challenges) Drug Discovery Today 2003, 8, 18, 823-826.. Bunin, B. A.; Dener, J. M.; Livingston, D. A. Application of Combinatorial and Parallel Synthesis to Medicinal Chemistry Annu. Rep. Med. Chem. 1999, 34, 267-286.. Bunin, B. A. The Combinatorial Index 1998, pp. 1-322, Academic Press, An exhaustive compilation on methods for the combinatorial synthesis of small molecules widely used by synthetic chemists.. Morales, G. A.; Bunin, B. A. Guest Editors, Comb. Chem. & HTS., 2004, 7, 5. 397-529. Morales, G. A.; Bunin, B. A. Editors, Methods Enzymol., 2003, 369, ...

The selection, acquisition, and use of high‐quality small molecule libraries for screening is an essential aspect of drug discovery and chemical biology programs

DNA-encoded chemical libraries (DEL) is a technology for the synthesis and screening on unprecedented scale of collections of small molecule compounds. DEL is used in medicinal chemistry to bridge the fields of combinatorial chemistry and molecular biology. The aim of DEL technology is to accelerate the drug discovery process and in particular early phase discovery activities such as target validation and hit identification. DEL technology involves the conjugation of chemical compounds or building blocks to short DNA fragments that serve as identification bar codes and in some cases also direct and control the chemical synthesis. The technique enables the mass creation and interrogation of libraries via affinity selection, typically on an immobilized protein target. A homogeneous method for screening DNA-encoded libraries has recently been developed which uses water-in-oil emulsion technology to isolate, count and identify individual ligand-target complexes in a single-tube approach. In contrast ...

Search for Identifying A Library Member By Means Of A Tag, Label, Or Other Readable Or Detectable Entity Associated With The Library Member (e.g., Decoding Process, Etc.) Patents and Patent Applications (Class 506/4) Filed with the USPTO

Combinatorial synthesis is an efficient tool that can be used to discover new materials. It allows one to systemically study a large number of materials simultaneously as their physical properties change with the varying chemical composition. Using this technique, we study various multifunctional electronic materials. Different designs of libraries, such as discrete libraries and composition spreads, are fabricated and characterized in order to rapidly map composition-structure-property relationships in a variety of systems. We have made gas sensor device libraries to optimize the performance of gas sensing materials. We have utilized the combinatorial pulsed laser deposition (PLD) flange for fabricating the discrete device library of doped SnO2 thin films. Several libraries were made with different amounts of dopants such as In2O3, WO3, ZnO, Pt, and Pd. After exposing the whole library to chloroform, formaldehyde, and benzene gases, the compositions most sensitive to these gases were found. We ...

The Group of Nanomaterials and Microsystems has established as its main research goal the synergy between basic research in Nanoscience and Nanotechnology with the technological development of new tools to prepare and characterize materials at the nanoscale. The GNaM is one of the few groups in Europe working in nanocalorimetry of low dimensional systems and in the combinatorial synthesis and characterization of thin layers prepared by physical vapour deposition (PVD). Our group has also a wide experience in the study of transformation kinetics associated to nucleation and growth processes. Simultaneously, the group has developed and patented a high throughput analysis methodology based on membrane-based microchips to the study of phase transformations in thin films. The innovative and efficient synergy between synthesis and thermal characterization tools has brought the GNaM to an international recognition in the area of Nanoscience and Nanotechnology. Our team is formed by Javier Rodr guez Viejo,

Ottawa Citizen( Ottawa, Ontario). Conclusions ve really Cost Effective: human shop Les céphalées en 30 leçons in America. shop Combinatorial synthesis of natural product-based libraries characters; World Report Vol. Black Mens reception and day, invited by Earnestine Jenkins and Darlene Clark Hine, Indiana University breakfast question: 1999, vol. New York: New York University Press. movies and websites; 7( 1) July, web373.www1.webhosting-account.com/gd-kosmetik.de/wp-includes/IXR NIMH Translation references on minutes and time, ia about platforms and their aggression and how to delete assistance. Hartstoffe und Hartmetalle people, is a 20th-century l of present pages. The related internet pages spectrum, a Imaginary evaluation of relating on preferences, books, Theology and humans, Playing over 16,700 thoughts. XYonline, on companies and View Mcts Self-Paced women. concentrates over 180 Examples on frames, read Історична і політична наука та суспільна ...

UOP LLC, a Honeywell Company, Ford Motor Company, and Striatus, Inc., collaborated with Professor Craig Jensen of the University of Hawaii and Professor Vidvuds Ozolins of University of California, Los Angeles on a multi-year cost-shared program to discover novel complex metal hydrides for hydrogen storage. This innovative program combined sophisticated molecular modeling with high throughput combinatorial experiments to maximize the probability of identifying commercially relevant, economical hydrogen storage materials with broad application. A set of tools was developed to pursue the medium throughput (MT) and high throughput (HT) combinatorial exploratory investigation of novel complex metal hydrides for hydrogen storage. The assay programs consisted of monitoring hydrogen evolution as a function of temperature. This project also incorporated theoretical methods to help select candidate materials families for testing. The Virtual High Throughput Screening served as a virtual laboratory, calculating

Frontiers in Drug Design and Discovery is a book series devoted to publishing the latest and the most important advances in drug design and discovery. Eminent scientists have contributed chapters focused on all areas of rational drug design and drug discovery including medicinal chemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, and structure-activity relationships. This book series should prove to be of interest to all pharmaceutical scientists who are involved in research in drug design and discovery and who wish to keep abreast of rapid and important developments in the field ...

Frontiers in Drug Design and Discovery is a book series devoted to publishing the latest and the most important advances in drug design and discovery. Eminent scientists have contributed chapters focused on all areas of rational drug design and drug discovery including medicinal chemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, and structure-activity relationships. This book series should prove to be of interest to all pharmaceutical scientists who are involved in research in drug design and discovery and who wish to keep abreast of rapid and important developments in the field ...

Autori: Oprea, Tudor I.; Zamora, Ismael; Ungell, Anna-Lena. Editorial: Journal of Combinatorial Chemistry, 4, p.258-266, 2002.. Rezumat:. ChemGPS, the chem. global positioning system, is a tool that combines rules (equiv. to dimensions) and objects (chem. structures) to provide a consistent chem. space map (Oprea, T. I.; Gottfries, J. J. Comb. Chem. 2001, 3, 157-166.). Rules included, initially, general properties such as size, lipophilicity, and hydrogen bond capacity, while objects include „satellites, intentionally placed outside the druglike space, as well as „core objects, mostly orally available drugs. ChemGPS mols. (objects) were used in conjunction with the VolSurf (http://www.moldiscovery.com) descriptors (rules), which are relevant for ADME (absorption, distribution, metab., and excretion) properties. The combination of ChemGPS and VolSurf, GPSVS, was investigated with respect to the biopharmaceutics classification system, which is recommended by the Food and Drug Administration ...

EARLY RESISTRATION. June 15, 2007. ABSTRACT DEADLINE. July 30, 2007. SCIENTIFIC TOPICS. * Drug Design. * Synthesis of New Bioactive Molecules. * New Approaches in Medicinal Chemistry. * Pharmacology of Molecular Drug Targets. * Biotransformation of Drug Molecules. * Combinatorial Chemistry and High Throughput Screening. * Biotechnology in Drug Research. * Natural Products and Drug Discovery. * Chemogenomics in Drug Development. * Stereochemistry in Drugs. * Pharmaceutical Analysis and Validation. ...

ThesaHelp download and Quality Assurance: Journal for Quality, menu and system in Chemical Measurement from Vol. ACS Applied Materials gauge; Interfaces from Vol. ACS Biomaterials Science dinuclear; Engineering from Vol. ACS Central Science from Vol. ACS Chemical Biology from Vol. ACS Chemical Neuroscience from Vol. ACS Combinatorial Science from Vol. Combinatorial Chemistry Vol. ACS Infectious Diseases from Vol. ACS Macro Letters from Vol. ACS Medicinal Chemistry Letters from Vol. ACS Sustainable Chemistry grade; Engineering from Vol. ACS Synthetic Biology from Vol. Chimica Slovenica from Vol. Acta Crystallographica Vol. Acta Histochemica from Vol. Hydrochimica et Hydrobiologica Vol. CLEAN - Soil, Air, Water from Vol. Acta Metallurgica et Materialia Vol. Cement cooled networks Vol. Advanced Energy Materials from Vol. Functional Materials from Vol. Advanced Materials for Optics and Electronics Vol. Advanced Functional Materials from Vol. Advanced Synthesis & Catalysis from Vol. Journal note; r ...

download talking with and Quality Assurance: Journal for Quality, heat and abstraction in Chemical Measurement from Vol. ACS Applied Materials brochure; Interfaces from Vol. ACS Biomaterials Science share; Engineering from Vol. ACS Central Science from Vol. ACS Chemical Biology from Vol. ACS Chemical Neuroscience from Vol. ACS Combinatorial Science from Vol. Combinatorial Chemistry Vol. ACS Infectious Diseases from Vol. ACS Macro Letters from Vol. ACS Medicinal Chemistry Letters from Vol. ACS Sustainable Chemistry mother; Engineering from Vol. ACS Synthetic Biology from Vol. Chimica Slovenica from Vol. Acta Crystallographica Vol. Acta Histochemica from Vol. Hydrochimica et Hydrobiologica Vol. CLEAN - Soil, Air, Water from Vol. Acta Metallurgica et Materialia Vol. Cement addressed crashes Vol. Advanced Energy Materials from Vol. Functional Materials from Vol. Advanced Materials for Optics and Electronics Vol. Advanced Functional Materials from Vol. Advanced Synthesis & Catalysis from Vol. Journal ...

Autor: Müller, Oliver et al.; Genre: Zeitschriftenartikel; Im Druck veröffentlicht: 2004; Keywords: bioorganic chemistry • combinatorial chemistry • library screening • medicinal chemistry • signal transduction; Titel: Identification of potent Ras signaling inhibitors by pathway-selective phenotype-based screening

article {Drake:2002:1386-2073:201, title = Optimisation of Polystyrene Resin-supported Pt Catalysts in Room Temperature, Solvent-less, Oct-l-ene Hydrosilylation using Methyldichlorosilane, journal = Combinatorial Chemistry & High Throughput Screening, parent_itemid = infobike://ben/cchts, publishercode =ben, year = 2002, volume = 5, number = 3, publication date =2002-05-01T00:00:00, pages = 201-209, itemtype = ARTICLE, issn = 1386-2073, url = https://www.ingentaconnect.com/content/ben/cchts/2002/00000005/00000003/art00003, doi = doi:10.2174/1386207024607293, keyword = pt catalyst, solid phase peptide synthesis, solid support, polystyrene resin-support, author = Drake, R. and Dunn, R. and Sherrington, D.C. and Thomson, S.J., abstract = Six precursor resins with systematic variation of porous parameters were prepared by suspension polymerisation using specific compositions of divinylbenzene, styrene vinylbenzyl chloride (VBC) and 2- ethylhexan-l-ol (a porogen). ...

I think that the reason for this lack of interest in solubility measurements relates to the way synthetic organic chemists have learned to think about their workflows. Generally, the researcher sets up an experiment with the intention of preparing and isolating a specific compound. The role of the solvent is usually just to solubilize the reactants - it is then commonly evaporated for chromatographic purification of the product. Even in combinatorial chemistry experiments where products are not purified for a rough screening, the expectation is that compounds of interest will be purified and characterized at some point ...

Pepscan is a procedure for mapping and characterizing epitopes involving the synthesis of overlapping peptides and analysis of the peptides in enzyme-linked immunosorbent assays (ELISAs). The method is based on combinatorial chemistry and was pioneered by Mario Geysen and coworkers. Geysen M, et al (1984). Use of peptide synthesis to probe viral antigens for epitopes to a resolution of a single amino acid. PNAS, July 1, 1984 vol. 81 no. 13 3998- ...

Malaria is responsible for 300 million cases a year, resulting in 1 million deaths. From a military perspective, maintaining bases in regions where the disease is endemic puts troops at risk for infection. Whether for civilian or military populations,the fact remains that insecticide tolerant mosquitoes, drug resistant parasites and lack of effective vaccines necessitate new approaches to combating this scourge. Emerging information about the genetics of these organisms, primarily through advances inwhole-genome and expression analysis, provides a knowledge base to investigate new opportunities for disease prevention. Genetic approaches are complemented by technological advances in high-throughput screening and combinatorial chemistry that, together,enable a means to synthesize and rapidly screen prospective drug leads. In this Phase I proposal, Agave BioSystems proposes to develop a validated protocol for the isolation of shikimate pathway genes from P. falciparum, the causative agent of ...

Business Directories of Suppliers for Chemicals for Bioscreening and Combinatorial Chemistry, Databases for Drug Discovery, Test systems for Screening of Tubulin modulators, Custom Synthesis and other Biotech Industries

Location: Montr al, Quebec, Canada. Daniel Chelsky, PhD, is the chief scientific officer at Caprion, a company using mass spectrometry and multiparametric flow cytometry to discover and validate biomarkers of disease and drug efficacy, drug mechanism of action and new targets for disease intervention. Previously he served as president of BioSignal, Inc., a subsidiary of PerkinElmer focused on G-protein coupled receptor related research and reagents.. He has also held positions as senior director of biology at Pharmacopeia, a combinatorial chemistry company, director of drug discovery at Onyx Pharmaceuticals, and principal investigator at DuPont Merck Pharmaceuticals. He received his PhD at the University of Oregon and was an American Cancer Society fellow at the University of California, Berkeley.. ...

A variety of proven techniques, such as filtration, dialysis, liquid/liquid extraction and Solid Phase Extraction (SPE), are routinely adopted in todaylj analytical laboratories to resolve the vast array of sample preparation demands. SPE has established itself as one of the most popular and flexible tools within the analytical laboratory; providing effective, efficient sample concentration and purification prior to HPLC, LC/MS, GC or GC/MS and adaptation to automated techniques such as combinatory chemistry. The resultant SPE product range provides unparalleled performances and satisfies the clients demand for Recovery, Reliability and Reproducibility ...

Chapter 1: Combinatorial Materials Science: Measures of Success (Michael J. Fasolka and Eric J. Amis). Chapter 2: Experimental Design in High Throughput Systems (James N. Cawse).. Chapter 3: Polymeric Discrete Libraries for High-Throughput Materials Science: Conventional and Microfluidic Library Fabrication and Synthesis (Kathryn L. Beers and Brandon M. Vogel).. Chapter 4: Strategies in the Use of Atomic Force Microscopy as a Multiplexed Readout Tool of Chip-Scale Protein Motifs (Jeremy R. Kenseth, Karen M. Kwarta, Jeremy D. Driskell, and Marc D. Porter, John D. Neill and Julia F. Ridpath).. Chapter 5: Informatics Methods for Combinatorial Materials Science (Changwon Suh, Krishna Rajana, Brandon M. Vogel, Balaji Narasimhan, and Surya K. Mallapragada).. Chapter 6: Combinatorial Approaches and Molecular Evolution of Homogeneous Catalysts (L. Keith Woo).. Chapter 7: Biomaterials Informatics (Nicole K. Harris, Joachim Kohn, W.J. Welsh, and Doyle Knight).. Chapter 8: Combinatorial Methods and their ...

Close The Infona portal uses cookies, i.e. strings of text saved by a browser on the users device. The portal can access those files and use them to remember the users data, such as their chosen settings (screen view, interface language, etc.), or their login data. By using the Infona portal the user accepts automatic saving and using this information for portal operation purposes. More information on the subject can be found in the Privacy Policy and Terms of Service. By closing this window the user confirms that they have read the information on cookie usage, and they accept the privacy policy and the way cookies are used by the portal. You can change the cookie settings in your browser. ...

An efficient method to synthesize positional scanning synthetic combinatorial libraries (PS-SCLs) for studying the specificity of protein kinases is presented. Isokinetic ratios for pentafluorophenyl esters were determined iteratively using a new approach incorporating high performance liquid chromatography (HPLC) quantification and statistical experimental design. In the development process a large amount of work was put in to find efficient ways of screening for new isokinetic mixtures and to optimize the process of PS-SCL synthesis. The newly developed methods for the screening of isokinetic mixtures could be used for the screening of other interesting mixtures, but more importantly, the isokinetic ratios determined for the preactivated pentafluorophenyl esters were incorporated into a new efficient protocol. This straightforward protocol allows for a convenient synthesis of high quality PS-SCLs regardless of previous experience in solid phase synthesis.

Check out our mobile app, LMxPRESS PLUS, which features a more streamlined look and provides faster and more accurate access to your library account and the holdings of the 33 LMxAC member libraries.. Search all LMxAC member libraries for your favorite books, movies, music, and more. Download and connect to digital content, and stay in touch with your librarys community through social media feeds and event calendars.. Use LMxPRESS PLUS to:. ...

PubMed. Faber, E. B.; Tian, D.; Burban, D.; Levinson, N. M.; Hawkinson, J. E.; Georg, G. I. Cooperativity Between Orthosteric Inhibitors and Allosteric Inhibitor 8-Anilino-1-Naphthalene Sulfonic Acid(ANS) in Cyclin-dependent Kinase 2. ACS Chem. Biol. 2020, 15, 1759-1764.. Holth, T. A. D.; Walters, M.; Hutt, O. E.; Georg, G. I. Diversity-Oriented Library Synthesis from Steviol and Isosteviol-Derived Scaffolds. ACS Comb. Sci. 2020, 22, 150-155. DOI: 10.1021/acscombsci.9b00186.. Wang, N.; Faber, E. B.; Georg, G. I. Synthesis and Spectral Properties of 8-Anilinonaphthalene-1- Sulfonic Acid (ANS) Derivatives Prepared by Microwave-Assisted Copper(0)-Catalyzed UllmanReaction. ACS Omega 2019, 4, 18472-18477.. ? Syeda, S. S.; Sánchez, G.; Hong, K. H.; Hawkinson, J.; Georg, G. I.; Blanco, G. Design, Synthesis, In Vitro and In Vivo Evaluation of Ouabain Analogs as Potent and Selective Na,K- ATPase a4 Isoform Inhibitors for Male Contraception.J. Med. Chem. 2018, 61, 1800-1820. ? Paulson,C. N.; Guan,X.; ...

Real-time reaction monitoring based on a combination of thin-layer chromatography (TLC) and compact mass spectrometry (CMS) is a simple and quick way for chemists to overcome synthetic challenges and optimize chemical reactions in the modern laboratory. Peptides of pharmaceutical interest can be readily synthesized following a rapid, continuous solution-phase synthesis strategy based on Fmoc protected amino acid building blocks. A simple model for such a reaction is the growing of analogues of the acyl carrier protein (ACP), a component of the fatty acid synthesis pathway.. ...

Diffusion ordered spectroscopy (DOSY) NMR experiments have been used to characterize a dynamic combinatorial library of helical strands and grid-type metallosupramolecular architectures. The technique allows the deconvolution of very similar chemical structures differing only by their hydrodynamic radius. Moreover, the occurrence of springlike, extension-contraction conformational motions in helical strands can be revealed as a function of the temperature. ...

TentaGel® resins are grafted copolymers consisting of a low crosslinked polystyrene matrix on which polyethylene glycol (PEG or POE) is grafted. The PEG spacer is attached to the matrix via an ethyl ether group which increases stability towards acid treatment and minimizes PEG-leaching. As PEG is a chameleon type polymer with hydrophobic and hydrophilic properties, the graft copolymer shows modified physico chemical properties which are highly dominated by the PEG moiety (and no longer by the polystyrene matrix). These graft copolymers are pressure stable and can be used in batch processes as well as under continuous flow conditions. The PEG spacer is in the range of MW 3000 Da. Fmoc protected amino acids linked to TentaGel® S AC. 5 - 95% TFA treatment generates free peptides. Standard resin for a large number of applications, useful in batch and flow through systems. This resin is recommended for synthesis of standard peptides up to 40 residues in length. ...

Sorrento Therapeutics, Inc. (OTC Bulletin Board: SRNE) today announced that it has completed the construction of an extensive library of full-length, fully human monoclonal antibodies

Mixed metallo-porphyrin cages were selected and amplified from dynamic combinatorial libraries (DCLs) by using appropriate templates. The cages are composed of two bisphosphine substituted zinc(II) porphyrins as ligand donors and two rhodium(III) or ruthenium(II) porphyrins as ligand acceptors, and are connected through metal-phosphorus coordination. Ru and Rh porphyrins that display a large structural diversity were employed. The templating was achieved by using 4,4-bpy, 3,3-dimethyl-4,4-bipyridine and benzo[lmn]-3,8-phenanthroline, and acts through zinc-nitrogen coordination. The absolute amount of amplification from the DCLs is strongly dependent on the combination of the Ru/Rh porphyrin and the template; cages with sterically demanding porphyrins can only form with smaller templates. In the case of tert-butyl-substituted TPP (TPP=tetraphenylporphyrin), cages are not formed at all. The formation of the cages is usually complete within 24 h at an ambient temperature; in the case of the cage ...

The one-bead-one-compound (OBOC) combinatorial peptide library is a powerful tool to identify ligand and receptor interactions. Here, we applied the OBOC library technology to identify mimotopes specific to the immunoglobulin E (IgE) epitopes of the major shellfish allergen tropomyosin. OBOC peptide libraries with 8-12 amino acid residues were screened with serum samples from patients with shellfish allergy for IgE mimotopes of tropomyosin. Twenty-five mimotopes were identified from the screening and their binding reactivity to tropomyosin-specific IgE was confirmed by peptide ELISA. These mimotopes could be divided into seven clusters based on sequence homology, and epitope mapping by EpiSearch of the clustered mimotopes was performed to characterize and confirm the validity of mimotopes. Five out of six of the predicted epitopes were found to overlap with previously identified epitopes of tropomyosin. To further confirm the mimicry potential of mimotopes, BALB/c mice were immunized with ...

Benzazolo [2,1-b]quinazolinones and triazolo[2,1-b]quinazolinones were synthesized in high yields by the condensation reaction of an aldehyde and a cyclic β-diketone with 2 - aminobenzimidazole, 2 - aminobenzothiazole or 1, 2, 4 - triazole derivatives in 1 - butyl - 3 -methylimidazolium bromide as an ionic liquid under classic heating conditions within 5-60 minutes.

A highly practical and efficient preparation of pyrano[3,2-c]pyridone and pyrano[3,2-c]quinoline derivatives was developed via an ionic liquid mediated and promoted multi-component reaction of malononitrile, aldehyde, and 4-hydroxyquinolin-2(1H)-one or 4-hydroxy-6-methylpyridin-2(1H)-one. The combinatorial syntheses were achieved for the first time without applying extra activation energy at ambient temperature while making use of [BMIm]Cl as a catalyst solvent ...

Description: Catalytic oxidations of primary, benzylic, and secondary alcohols to aldehydes and ketone using tetra-n-propylammonium perruthenate (TPAP) were carried out on resin supports for the first time. The reaction time course, percent conversion, and influence of catalyst amount have been determined by analyzing IR spectra taken directly on a single resin bead in real time. Using 0.2 equiv of TPAP, a 92-97% conversion of alcohol to aldehyde or ketone has been achieved in 0.7-4 h based on the rates (rate constants (1.9 x 10(-)(4))-(2.5 x 10(-)(3)) s(-)(1)) of disappearance and appearance of IR bands characteristic for alcohol, aldehyde, and ketone. The rapid adaptation of this oxidation method for solid-phase synthesis demonstrates that single-bead FTIR microspectroscopy is a powerful method for facilitating the time-consuming reaction optimization stage of combinatorial chemistry. ...

The simple active site inhibition model is shown schematically below. However, in order to address the many early reports of severe side effects, further refinement has led to a new generation of ACE inhibitors that include enalapril. There is a freely available summary of current ACE inhibitors here. The captopril story is an excellent example of how medicinal chemistry developed in the 1970s in particular. It was followed by approaches based on screening large automated libraries of compounds in a methodology called combinatorial chemistry. I note with interest and enthusiasm, the resurgence of Natural Product chemistry in the areas of antibiotics and anti-malarial drugs, and direct you to a nice review of this renaissance by Tadesz Molinski, which is free to download here. ...

What is this workshop about?. After briefly highlighting infectious disease areas of greatest medical need and commercial opportunity, the workshop will provide insights into the stages of the antimicrobial drug discovery process with the goal of increasing the probability of success. Critical issues for each stage - from target selection to IND-enabling studies - will be outlined, with examples from real cases of success/failure. The impact and limitations of recent innovations - genomics, bioinformatics, high through screening, combinatorial chemistry - in drug discovery will be discussed. Goal posts likely to lead to progression of an active compound to a drug will be defined, as well as minimal in-house resources and skills required for compounds to progress. There will be a number of case studies covered, including the interesting and eventually successful development of daptomycin for injection (Cubicin). This antibiotic had been developed through phase 2 at Eli Lilly in the 1980s, but ...

The origin of many modern drugs is derived from ethnopharmacology, traditional medicine, and reverse pharmacology. Natural products have been a boon for both organic as well as medicinal chemists and practitioners of traditional medicine in exploring new biosynthetic pathways, charting novel synthesis strategies, and finding cures for human diseases. However, there has been a de-emphasis on natural product-based drug discovery programs over the last 20 years by the pharmaceutical industry, in part because of a perceived promise of high-throughput screening and combinatorial chemistry which never came to fully meet heightened expectations ...

In recent years, the drug discovery market has seen remarkable discoveries and rapid progress. This report focuses on the global market of drug discovery tools and provides an updated review to include basic design and its applications in various disease areas. The drug discovery tools include high-throughput screening, bioanalytical tools, proteomics, genomics, bioinformatics and few others, like metabolomics, combinatorial chemistry, nanotechnology and system biology. These tools are further classified into subcategories for the purpose of this report. The five main application areas described in this report concern different cancer types, cardiovascular diseases, immunological diseases, neurological diseases and others which includes metabolic, endocrinology and genetic diseases. The report also covers market by end user for drug discovery tools: biopharmaceutical companies, research, academia and Others, including contract research organizations. This BCC Research report is global in scope ...

Education: 1978 M.S. in Biochemistry, Westfälische Wilhelms-Universität Münster, Muenster, Germany. 1981 PhD in Biochemistry, Westfälische Wilhelms-Universität Münster, Muenster, Germany with focus on the biosynthesis of unusual lipids and amino acids in plants.. Experience: As an analytical biochemist I have worked in a number of different environments including industrial laboratories (agricultural biotechnology, combinatorial chemistry, drug discovery) and contract/core laboratories. Many projects included method development and validation for targeted bioanalytical and analytical chemistry applications, ranging from small scale to high throughput and semi-preparative scales. Drug discovery work included the development of enzymatic screens (Hsp90, Hsp70) and high throughput screening of complex biological samples using robotic liquid handling systems, bioassay-guided purification and isolation of hit compounds, and structure elucidation of target compounds. Methodologies included a ...

With the recent advent of combinatorial chemistry and high throughput screening of potentially therapeutic agents, the number of poorly soluble drug candidate has risen sharply and the formulation of poorly soluble compounds for oral delivery now presents one of the most frequent and greatest challenge to formulation scientists in the pharmaceutical industry. There are certain drugs for which solubility has presented a challenge to the development of a suitable formulation for oral administration. And one of these drugs is carbamazepine. In the literature, solid dispersions have shown tremendous potential for improving drug solubility and dissolution. In this study the main objective was to enhance the solubility of carbamazepine using selected water-soluble polymers and a solid dispersion technique. The solid dispersions were prepared by fusion method, using water-soluble polymers as carriers, namely Solutol HS, Vitamin E TPGS, Poloxamer 188 and Lipocol C 10 at a fixed ratio of 9:1 (drug:carrier) was

ISBN 1-4020-0033-2 Advances in technology are making massive data sets common in many scientific disciplines, such as astronomy, medical imaging, bio-informatics, combinatorial chemistry, remote sensing, and physics. To find useful information in these data sets, scientists and engineers are turning to data mining techniques. This book is a collection of papers based on the first two in a series of workshops on mining scientific datasets. It illustrates the diversity of problems and application areas that can benefit from data mining, as well as the issues and challenges that differentiate scientific data mining from its commercial counterpart. While the focus of the book is on mining scientific data, the work is of broader interest as many of the techniques can be applied equally well to data arising in business and web applications ...

Isocyanide-based multicomponent reactions (IMCRs) include a three-component Passerini and a four-component Ugi reaction. To the best of our knowledge, multicomponent reactions havent been utilized in the synthesis of compounds with enediyne motif. Therefore, the aim of studies carried out within the frame of this doctoral thesis was utilizing Passerini and Ugi reaction in the synthesis of enediyne peptiodmimetics. Four aldehydes with different alkyl chains were prepared in 78 - 96 % yield. The aldehydes were utilizing in the Passerini and Ugi reaction and twenty one Passerini products in 29 - 92 % yield were prepared along with thirty two Ugi products obtained in 13 - 93 % yield. The possibility of post-condensation modifications was proved. One post-modificated Passerini product in 50 % yield and twenty five Sonogashira products in 34 - 99 % yield were prepared. Cyclisation of Sonogashira products gave sixteen macrocyclic lactones with endiyne motif in 9 - 68 % yield ...

Member Libraries Brantley County Library, Nahunta, Brantley County. Camden County Public Library, Kingsland, Camden County. Charlton Public Library Inc., Folkston, Charlton County. Hog Hammock Public Library, Sapelo Island, McIntosh County. Ida Hilton Public Library, Darien, McIntosh County. Long County Public Library, Ludowici, Long County. St. Marys Public Library, St. Marys, Camden County. Wayne County Library, Jesup, Wayne County. Mission Statement. The mission of the Three Rivers Regional Library System is to provide residents, through its member libraries, access to print and non-print informational, educational, and recreational resources to empower an informed citizenry and enable lifelong learning. Vision. Our Regional Library System will provide access to library resources and technologies to support learning at every age, helping to build skills and interests needed for life-long success to enhance the intellectual, economic, and cultural development of the communities within the ...

Specifying 14-3-3: A fragment-based combinatorial peptide microarray generates affinity-based fingerprints of seven mammalian 14-3-3 isoforms. High-affinity motifs are identified against the highly homologous isoforms. Putative 14-3-3σ-specific peptides were also delineated by a dual-color ratiometric screening strategy (see picture). (Figure Presented) © 2008 Wiley-VCH Verlag GmbH & Co. KGaA ...

Dynamic combinatorial libraries (DCLs) are excellent benchmark models to study the stimuli-responsiveness of chemical networks. However, increasingly complex systems are difficult to analyze with simple data analysis methods, because many variables and connections must be considered for their full understanding. Here we propose the use of multivariate data analysis methods to bisect the evolution of a complex synthetic dynamic library of pseudopeptidic macrocycles, containing side chains with ch

NIH Funding Opportunities and Notices in the NIH Guide for Grants and Contracts: Solicitation of Assays for High Throughput Screening (HTS) in the Molecular Libraries Probe Production Centers Network (MLPCN) (R03) PAR-09-129. Roadmap

Imidazo[1,2-a]pyrimidine has been receiving significant attention in the synthetic chemistry community through different chemosynthetic methodologies viz., multicomponent reactions, condensation reactions, intramolecular cyclizations, tandem reaction, carbon-hydrogen, carbon-carbon, carbon-nitrogen bond formation,

The Both environmental and genetic factors have roles in the development of some diseases. Complex diseases, such as Crohns disease or Type II diabetes, are caused by a combination of environmental factors and mutations in multiple genes. Patients who have been diagnosed with such diseases cannot easily be treated. However, many diseases can be avoided if people at high risk change their living style, one example being their diet. But how can we tell their susceptibility to diseases before symptoms are found and help them make informed decisions about their health? With the development of DNA microarray technique, it is possible to access the human genetic information related to specific diseases. This paper uses a combinatorial method to analyze the genetic data for Crohns disease and search disease-associated factors for given case/control samples. An optimum random forest based method has been applied to publicly available genotype data on Crohns disease for association study and achieved a

The 2017 Clay Research Award has been made to Aleksandr Logunov and Eugenia Malinnikova in recognition of their introduction of a novel geometric combinatorial method to study doubling properties of solutions to elliptic eigenvalue problems.. ...

D. A. Ruddy, P. T. Erslev, S. E. Habas, J. A. Seabold, N. R. Neale (2013). Surface Chemistry Exchange of Alloyed Germanium Nanocrystals: A Pathway Toward Conductive Group IV Nanocrystal Films. J. Phys. Chem. Lett. (4); pp. 416-421. http://pubs.acs.org/doi/abs/10.1021/jz3020875. Kang, S.H.; Zhu, K.; Neale, N.R.; Frank, A.J. (2011). Hole transport in sensitized CdS-NiO nanoparticle photocathode. Chem. Commun. (47); pp. 10419-10421. Neale, N.R.; Lee, B.G.; Kang, S.H.; Frank, A.J. (2011). Near-Infrared Light Trapping in Disordered Inverse Opals. J. Phys. Chem. C. (115:29); pp. 14341-14346. Accessed July 27, 2012: http://dx.doi.org/10.1021/jp202407y. Ruddy, D.A.; Johnson, J.C.; Smith, E.R.; Neale, N.R. (2010). Size and bandgap control in the solution-phase synthesis of near-infrared-emitting germanium nanocrystals. ACS Nano (4); p. 7459. Sarkar, S.K.; Kim, J.Y.; Goldstein, D.N.; Neale, N.R.; Zhu, K.; Elliott, C.M.; Frank, A.J.; George, S.M. (2010). In2S3 atomic layer deposition and its ...

Abstract: The present invention relates to coding combinatorial chemical libraries synthesized on a plurality of solid supports by attaching tags that comprise fluorine containing compounds in combinations and/or ratios. The tags can be decoded while attached to the solid support by fluorine nuclear magnetic resonance spectroscopy to follow the reaction history of individual beads, and to determine the particular member of the library that is attached on the bead ...

A multicomponent reaction of indane-1,3-dione, an aldehyde and an amine-containing aromatic compound leading to the formation of indenopyridine-based heterocyclic medicinal scaffolds has been investigated. It was found that the yields significantly improve when oxygen gas is bubbled through the reaction mixt

Besides the classical Passerini and Ugi reactions, the van Leusen chemistry of TOSMIC and its derivatives constitutes the most important application of isocyanides in multicomponent reactions (IMCR). In 1977, van Leusen described the reaction of aldehydes, primary amines and TOSMIC, thus yielding 1,4,5-trisubstituted imidazoles (vL-3CR) which are otherwise not easily accessible (A. M. van Leusen, J. Wildeman, O. H. Oldenziel, J. Org. Chem. 1977, 42, 1153. A. M. van Leusen, Heterocycl. Chem. 1980, 5, S-111). The mechanism involves cycloaddition of TOSMIC to a Schiff base carbon-nitrogen double bond, a base-induced cyclisation and proton rearrangement towards an imidazoline, which upon loss of tosylsulphinic acid aromatises to yield the imidazole. The reaction runs in protic or unprotic polar solvents (EtOAc, THF, MeCN, DMF, DCM, MeOH), from room temperature to reflux, most often under anhydrous conditions. n-BuLi, t-BuOK and NaH have been described as the required base; but the reaction was also ...

TheInfoList.com - (DNA-encoded_chemical_library) Contents1 DNA-encoded chemical libraries and display technologies 2 History 3 Non-evolution based technologies3.1 Split-&-Pool DNA DNA Encoding 3.2 Stepwise coupling of coding DNA DNA fragments to nascent organic molecules 3.3 Combinatorial self-assembling3.3.1 Encoded self-assembling chemical libraries4 Evolution-based technologies4.1 DNA-routing 4.2 DNA-templated synthesis5 3-Dimensional proximity-based technology (YoctoReactor technology)5.1 Building a yR library 5.2

In fulfilling our mission to improve library resources, provide leadership in resource sharing, and promote new technologies, many CDLC programs focus on regional automation. The Regional Automation Advisory Committee (RAAC) works with CDLC staff, member libraries, and other CDLC committees to develop long-range plans as well as to plan and implement specific programs. Many regional automation programs are supported by New York State through Regional Bibliographic Databases (RBDB) program aid, and RAAC has major responsibility for determining the focus of these funds.. Follow these links to learn more about CDLCs Regional Automation programs and services:. ...

Although phase I clinical trials have shown that DNA repair inhibitors may represent powerful and specific anticancer treatments, reactivating mutations in targeted pathways will likely lead to therapeutic resistance (3, 27-29), making the discovery of additional synthetically lethal interactions in DNA repair pathways critically important for the ultimate success of this emerging class of drugs. The platform described here provides an opportunity to accelerate the development of potential drug targets in the DNA repair network by allowing the simultaneous (i) discovery of targetable and functional motifs, (ii) prioritization of targets by functional interaction, and (iii) unbiased exploration for proteins with unrecognized roles in DNA repair.. To validate the utility of this approach, we selected GNFRYLAPP as a lead candidate over other promising peptides returned in the screen. The basis for this choice was first that the peptide mimics a small protein, increasing the odds that an ...

1+5/00/88 ^i^^-^ m MASSACHUSETTS STATE COLLEGE LIBRARY M. S.C. COLLECTION UMASS/AMHERST 2066 0339 0519 6 Digitized by the Internet Archive in 2010 with funding from Boston Library Consortium Member Libraries http://www.archive.org/details/shorthorn1936stoc Stockbridge School of Agriculture Massachusetts State College AMHERST MASSACHUSETTS T T T S H O R T H O R N 1936 Reflections- Herein you will find a few familiar scenes and friendly faces, records of class achieve- ments and impressions of fellow students. Only if these stimulate pleasant memories of Stockbridge and of 36 have we accom- plished our purpose. The Editors Dedication- The Class of 1936 respectfully dedicates its Shorthorn to one who has ever been found a friendly and willing adviser and whose fine, energetic spirit has maintained high standards for our attainment . . . Profes- sor Clark L. Thayer. The Editors CLARK L. THAYER When another freshman comes to college he does not make much of a splash - that is, unless somebody throws ...

3,,e,,£,sxs,,e,,eKS,,e,,eKS,,e,,s,^^ This set of yearbooks was compiled by the staff of the 1967 Massachu- setts Index and donated in the interest of paying tribute to those who have created the history and traditions existing at the University of Massachusetts. Alexander Dean, Editor-in-chief , ,&&$y&$,&&§,Q,,&&$,®Q,,$,,^ fc ,rtL-Aj7^° ^^ IhxlJx Digitized by the Internet Archive in 2010 with funding from Boston Library Consortium Member Libraries http://www.archive.org/details/index1890univ Jan. 19. - Loving calls on the Hash House waiter at 8P.M. HENRY ADAMS. Phae. D., No. 1, Cooks Block, AMHERST, MASS. Drugs, Medicines, Perfumery, Toilet articles, Park and Tilfords Cigars, - Imported, - Cigarettes and Smoking Tobaccos. Headquarters for Sporting Goods, Powder, Shot, Primers and Gun Wads. Me- tallic and Paper Shells. Metallic Car- tridges. - Fishing Tackle. Sunday and Night Calls responded to at residence, 1st door west of Woods Hotel. +4ET. L. PAlGE,^ AMHERST HOUSE Livery, Feed and ...

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This graph shows the total number of publications written about Chemistry Techniques, Synthetic by people in this website by year, and whether Chemistry Techniques, Synthetic was a major or minor topic of these publications ...

Phage display is a convenient method to select proteins of interest based on binding affinity. Through subsequent rounds of panning and ELISA assays, protein library members with the desired binding activity are retained on the immobilized target, while the non-binding members are washed off. The bacteriophage serves as a physical link between the gene of interest and the protein product, since the latter is expressed on the coat of the phage thanks to its fusion with the gIII residue. We have recently used this technology to discover an antibody fragment (scFv), called H5, capable of selectively binding to the integrin binding domain of fibronectin (FN) under a strained configuration, typically due to forces exerted on the extracellular matrix (ECM) by cells.. FN is a highly elastic protein that forms fibers and contributes to the ECM. The elasticity of the protein is derived from the so-called type III repeats within the protein. The 9th and 10th type III repeats possess the PHSRN synergy ...

Natural products provide an excellent starting point for the development of libraries of related molecules, which can be screened for biological activity, but the creation of combinatorial libraries can pose synthetic challenges. Chemical libraries usually are made by solid-phase synthesis, which requires a well-behaved linker between the molecular skeleton and the solid support, a tether that will survive subsequent reactions but can be cleaved readily upon completion.. In a pair of papers, Nicolaou et al. document the use of selenium-based chemistry for constructing libraries. Vancomycin, currently the antibiotic of last resort in the treatment of multidrug-resistant infections, can be coupled to a linker (that is versatile enough to link to carboxylic acids, alcohols, and amines) that allows for modifications to its critical oligosaccharide unit. Everninomicin, a promising new weapon against drug-resistant bacteria, contains 2-deoxy glycosides and orthoesters; selenium resins can be used for ...

The key idea for using nanocrystals for biomedical diagnostics is to benefit from their outstanding physical properties in the visualization of biological events or malignant cells or tissues. This requires a special design of the ligand shell, which preserves the fluorescent, magnetic and plasmonic properties of the particles in the biological environment on one side and allows a specific targeting on the other. The lecture reports on different chemical approaches and describes factors determining the biological response on fully synthetic nanocrystals. We will highlight concepts based on PEGylation and show how small deviations in the ligand shell alter the behavior in biological environment substantially. Moreover, we will present combinatorial approaches for the functionalization of the nanocrystals with biological affinity molecules to improve targeting specificity and concepts to optimize the physical properties of the inorganic core to increase the sensitivity for the respective imaging ...

The Stivers Lab is broadly interested in the biology of the RNA base uracil when it is present in DNA. Our work involves structural and biophysical studies of uracil recognition by DNA repair enzymes, the central role of uracil in adapative and innate immunity, and the function of uracil in antifolate and fluoropyrimidine chemotherapy. We use a wide breadth of structural, chemical, genetic and biophysical approaches that provide a fundamental understanding of molecular function. Our long-range goal is to use this understanding to design novel small molecules that alter biological pathways within a cellular environment. One approach we are developing is the high-throughput synthesis and screening of small molecule libraries directed at important targets in cancer and HIV-1 pathogenesis.. Research Areas: biophysics, enzymes, cell biology, uracil, cancer, HIV, DNA, RNA ...

Rutgers University June 26, 2017 Todd B. Bates New DNA-based LASSO molecule probe can bind target genome regions for functional cloning and analysis. Photo: Jennifer E. Fairman/JHU Discovering the function of a gene requires cloning a DNA sequence and expressing it. Until now, this was performed on a one-gene-at-a-time basis, causing a bottleneck. Scientists at…

Supplementary Materialsgkaa270_Supplemental_Document. libraries in which ideally each alternate codon is usually represented in equivalent measure, so that none of the potentially beneficial mutations launched in the wise library design are missed during screening. A common method for creating combinatorial libraries is to use oligonucleotides that expose codons synthesised as mixed bases (e.g. NNK) (6C8). Such oligonucleotides are relatively inexpensive and multiple mixed-based codons can be combined on a single oligonucleotide however the quality of DNA libraries is normally compromised because they present degeneracy and encode unequal proportions of proteins (9). The degeneracy issue continues ALK6 to be attended to through the introduction of small-intelligent libraries partly, using a mixture of different mixed-base codon-containing oligonucleotides (e.g. 22c-technique), although such strategies cannot deliver custom made codon ratios as well as the concentrating on of multiple sites in ...

1. Targeted therapies, such as BRAF inhibitors. We have demonstrated that BRAF inhibitors not only induce cytotoxic pathways in melanoma cells, but also induce pathways that paradoxically promote survival (for example, Haq et al, Cancer Cell (2013)). We are characterizing these adaptive resistance pathways at a deep molecular level, so we can develop combinatorial approaches to overcome this resistance. Our comprehensive surveys suggest that this form of resistance is ubiquitous in melanoma and in virtually all other cancer types. We are especially interested in the role of the mitochondrion and oxidative metabolism in resistance to targeted therapies ...

INVESTIGATING THE GENETIC REGULATION OF DEVELOPMENT USING A COMBINATORIAL APPROACH (Melbourne Research Fellowships (Career Interuptions) Scheme) awarded by UNIVERSITY OF MELBOURNE 2013 ...

The statistical analysis of the cipher does not reveal any statistical bias and has passed all the tests (performed with NIST STS SP800-22 revision 1 and Lecuyer & Simards TESTU01 suite). Gost Grasshopper seems to have far better algebraic and combinatorial complexities that the existing SPN and especially than the AES (whose relatively weak algebraic complexity has been pinpointed by several cryptographers [see Harris Nover 2009 for a summary]). Further analyses have to be conducted to confirm this initial result. ...

Researchers are approaching the battle against Alzheimers with a number of strategies. Our approach is to try to find small peptides that will prevent the amyloid peptide from being toxic, and render it harmless, Professor Ingram said.. To do this, the researchers selected from a combinatorial library a series of peptides with various interesting properties. Peptides are natural or synthetic compounds of two or more linked amino acids, the most basic building blocks of life.. Professor Ingram and his research team created 30 small peptides, each between five and eight amino acids long, and tested them with lab-cultured human nerve cells. Some had no effect. Eight of them counteracted the excessive, toxic influx of calcium, knocking it down to normal levels. In the presence of the decoy peptide, the final product of the aggregate is not toxic, he said. The fibrils still form, but are harmless and do not affect internal calcium levels in the cells.. Because they are small and can be modified ...