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Dynamic combinatorial chemistry

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https://www.readbyqxmd.com/read/28644617/dynamic-covalent-chemistry-of-carbon-dioxide-opportunities-to-address-environmental-issues
#1
Jean Septavaux, Geoffroy Germain, Julien Leclaire
Extraction and purification of basic chemicals from complex mixtures has been a persistent issue throughout the development of the chemical sciences. The chemical industry and academic research have grown over the centuries by following a deconstruction-reconstruction approach, reminiscent of the metabolism process. Chemists have designed and optimized extraction, purification, and transformation processes of molecules from natural deposits (fossil fuels, biomass, ores), in order to reassemble them into complex adducts...
June 23, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28640998/oximes-and-hydrazones-in-bioconjugation-mechanism-and-catalysis
#2
Dominik K Kölmel, Eric T Kool
The formation of oximes and hydrazones is employed in numerous scientific fields as a simple and versatile conjugation strategy. This imine-forming reaction is applied in fields as diverse as polymer chemistry, biomaterials and hydrogels, dynamic combinatorial chemistry, organic synthesis, and chemical biology. Here we outline chemical developments in this field, with special focus on the past ∼10 years of developments. Recent strategies for installing reactive carbonyl groups and α-nucleophiles into biomolecules are described...
June 22, 2017: Chemical Reviews
https://www.readbyqxmd.com/read/28480991/unraveling-the-multistimuli-responses-of-a-complex-dynamic-system-of-pseudopeptidic-macrocycles
#3
Angel M Valdivielso, Francesc Puig-Castellví, Joan Atcher, Jordi Solà, Romà Tauler, Ignacio Alfonso
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 charges of different sign...
May 8, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28451282/fluorogenic-sensor-platform-for-the-histone-code-using-receptors-from-dynamic-combinatorial-libraries
#4
Brendan C Peacor, Christopher M Ramsay, Marcey L Waters
Post-translational modifications (PTMs) on histone tails act in diverse combinations in the 'histone code' to control gene expression, with dysregulation observed in a variety of diseases. However, detection and sensing methods are limited, expensive, and/or low-throughput, including MS and antibody based detection. We found that by combining four synthetic receptors developed by dynamic combinatorial chemistry (DCC) in an indicator displacement system, we are able to create a pattern-based sensor platform that can discriminate single PTMs such as methylation and acetylation on a representative histone peptide with 100% accuracy as well as peptides bearing both dimethyl and trimethyl lysine in the presence of arginine methylation, which has not previously been demonstrated, and can even correctly distinguish the position of lysine methylation individually or in the presence of other PTMs...
February 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28440073/antiparallel-dynamic-covalent-chemistries
#5
Bartosz M Matysiak, Piotr Nowak, Ivica Cvrtila, Charalampos G Pappas, Bin Liu, Dávid Komáromy, Sijbren Otto
The ability to design reaction networks with high, but addressable complexity is a necessary prerequisite to make advanced functional chemical systems. Dynamic combinatorial chemistry has proven to be a useful tool in achieving complexity, however with some limitations in controlling it. Herein we introduce the concept of antiparallel chemistries, in which the same functional group can be channeled into one of two reversible chemistries depending on a controllable parameter. Such systems allow both for achieving complexity, by combinatorial chemistry, and addressing it, by switching from one chemistry to another by controlling an external parameter...
May 17, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28380234/the-lock-is-the-key-development-of-novel-drugs-through-receptor-based-combinatorial-chemistry
#6
REVIEW
Nikola Maraković, Goran Šinko
Modern drug discovery is mainly based on the de novo synthesis of a large number of compounds with a diversity of chemical functionalities. Though the introduction of combinatorial chemistry enabled the preparation of large libraries of compounds from so-called building blocks, the problem of successfully identifying leads remains. The introduction of a dynamic combinatorial chemistry method served as a step forward due to the involvement of biological macromolecular targets (receptors) in the synthesis of high affinity products...
2017: Acta Chimica Slovenica
https://www.readbyqxmd.com/read/28197313/from-dynamic-combinatorial-chemistry-to-in-vivo-evaluation-of-reversible-and-irreversible-myeloperoxidase-inhibitors
#7
Jalal Soubhye, Michel Gelbcke, Pierre Van Antwerpen, François Dufrasne, Mokhtaria Yasmina Boufadi, Jean Nève, Paul G Furtmüller, Christian Obinger, Karim Zouaoui Boudjeltia, Franck Meyer
The implementation of dynamic combinatorial libraries allowed the determination of highly active reversible and irreversible inhibitors of myeloperoxidase (MPO) at the nanomolar level. Docking experiments highlighted the interaction between the most active ligands and MPO, and further kinetic studies defined the mode of inhibition of these compounds. Finally, in vivo evaluation showed that one dose of irreversible inhibitors is able to suppress the activity of MPO after inducing inflammation.
February 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27829920/dna-functionalization-by-dynamic-chemistry
#8
Zeynep Kanlidere, Oleg Jochim, Marta Cal, Ulf Diederichsen
Dynamic combinatorial chemistry (DCC) is an attractive method to efficiently generate libraries of molecules from simpler building blocks by reversible reactions under thermodynamic control. Here we focus on the chemical modification of DNA oligonucleotides with acyclic diol linkers and demonstrate their potential for the deoxyribonucleic acid functionalization and generation of libraries of reversibly interconverting building blocks. The syntheses of phosphoramidite building blocks derived from D-threoninol are presented in two variants with protected amino or thiol groups...
2016: Beilstein Journal of Organic Chemistry
https://www.readbyqxmd.com/read/27526041/four-simultaneously-dynamic-covalent-reactions-experimental-proof-of-orthogonality
#9
Helen M Seifert, Karina Ramirez Trejo, Eric V Anslyn
Dynamic covalent reactions are widely used in dynamic combinatorial chemistry. Most of these reactions are run under differing reaction conditions and exhibit cross-reactivity when components of multiple reactions are present in one reaction vessel. Herein, we report the study of four dynamic covalent reactions that react reversibly under identical reaction conditions and do not exhibit any cross-reactivity. Dynamic behavior was shown via (1)H NMR based exchange experiments. Computational deconvolution of (1)H NMR spectra containing the components for more than one of the orthogonal reactions allowed for a semiquantitative analysis of the complex mixtures formed, showing that the reactions proceed independently of each other...
August 31, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27438816/protein-directed-dynamic-combinatorial-chemistry-a-guide-to-protein-ligand-and-inhibitor-discovery
#10
REVIEW
Renjie Huang, Ivanhoe K H Leung
Protein-directed dynamic combinatorial chemistry is an emerging technique for efficient discovery of novel chemical structures for binding to a target protein. Typically, this method relies on a library of small molecules that react reversibly with each other to generate a combinatorial library. The components in the combinatorial library are at equilibrium with each other under thermodynamic control. When a protein is added to the equilibrium mixture, and if the protein interacts with any components of the combinatorial library, the position of the equilibrium will shift and those components that interact with the protein will be amplified, which can then be identified by a suitable biophysical technique...
July 16, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27400756/fragment-linking-and-optimization-of-inhibitors-of-the-aspartic-protease-endothiapepsin-fragment-based-drug-design-facilitated-by-dynamic-combinatorial-chemistry
#11
Milon Mondal, Nedyalka Radeva, Hugo Fanlo-Virgós, Sijbren Otto, Gerhard Klebe, Anna K H Hirsch
Fragment-based drug design (FBDD) affords active compounds for biological targets. While there are numerous reports on FBDD by fragment growing/optimization, fragment linking has rarely been reported. Dynamic combinatorial chemistry (DCC) has become a powerful hit-identification strategy for biological targets. We report the synergistic combination of fragment linking and DCC to identify inhibitors of the aspartic protease endothiapepsin. Based on X-ray crystal structures of endothiapepsin in complex with fragments, we designed a library of bis-acylhydrazones and used DCC to identify potent inhibitors...
August 1, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27400283/discovery-of-novel-anti-hiv-agents-via-cu-i-catalyzed-azide-alkyne-cycloaddition-cuaac-click-chemistry-based-approach
#12
REVIEW
Ping Gao, Lin Sun, Junsu Zhou, Xiao Li, Peng Zhan, Xinyong Liu
INTRODUCTION: In recent years, a variety of new synthetic methodologies and concepts have been proposed in the search for new pharmaceutical lead structures and optimization. Notably, the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry approach has drawn great attention and has become a powerful tool for the generation of privileged medicinal skeletons in the discovery of anti-HIV agents. This is due to the high degree of reliability, complete specificity (chemoselectivity and regioselectivity), mild conditions, and the biocompatibility of the reactants...
September 2016: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/27265568/tetrameric-psuedo-peptide-receptors-with-allosteric-properties
#13
Mee-Kyung Chung, Stephen J Lee, Marcey L Waters, Michel R Gagné
This paper reports the binding properties of tetrameric pseudo-peptide receptors for protonated cytidines. The receptors, which were isolated from a dynamic combinatorial chemistry (DCC) experiment, bind the analytes with affinities that depend on the presence or absence of excess acid, and with a stoichiometry that is both concentration and temperature dependent.
June 21, 2016: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/26990904/dithioacetal-exchange-a-new-reversible-reaction-for-dynamic-combinatorial-chemistry
#14
A Gastón Orrillo, Andrea M Escalante, Ricardo L E Furlan
Reversibility of dithioacetal bond formation is reported under acidic mild conditions. Its utility for dynamic combinatorial chemistry was explored by combining it with orthogonal disulfide exchange. In such a setup, thiols are positioned at the intersection of both chemistries, constituting a connecting node between temporally separated networks.
May 10, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/26935941/probing-the-geometric-constraints-of-rna-binding-via-dynamic-covalent-chemistry
#15
John D McAnany, John P Reichert, Benjamin L Miller
Dynamic Combinatorial Chemistry (DCC) has proven to be a reliable method for identifying hit compounds for target nucleic acid (DNA and RNA) sequences. Typically, these hit compounds are subjected to a lengthy process of optimization via traditional medicinal chemistry. Here, we examine the potential of DCC to also generate and test variations on a hit compound as a method for probing the binding site of an RNA-targeted compound. Specifically, we demonstrate that addition of linker dithiols to a disulfide library containing a known binder to the HIV-1 frameshift-stimulatory RNA (a critical regulator of the HIV life cycle) can yield a mixture of new bridged structures incorporating the dithiol, depending on dithiol structure...
September 1, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/26920800/identification-of-inhibitors-for-vascular-endothelial-growth-factor-receptor-by-using-dynamic-combinatorial-chemistry
#16
Zhao Yang, Zheng Fang, Wei He, Zhixiang Wang, Haifeng Gan, Qitao Tian, Kai Guo
The novel analysis method consisting of size-exclusion chromatography (SEC) and HRMS analysis was firstly applied in the discovery of potential inhibitors towards cancer drug targets. With vascular endothelial growth factor receptor (VEGFR-2) as a target, dynamic combinatorial libraries (DCLs) were prepared by reacting aldehydes with amines. Four sensitive binders targeted VEGFR-2 were directly isolated from the library. Antitumor activity test in vitro and inhibition experiments toward angiogenesis were also carried out...
April 1, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/26651853/single-tailed-lipidoids-enhance-the-transfection-activity-of-their-double-tailed-counterparts
#17
Yihang Wu, Linxian Li, Qing Chen, Yi Su, Pavel A Levkin, Gary Davidson
Cationic lipid-like molecules (lipidoids) are widely used for in vitro and in vivo gene delivery. Nearly all lipidoids developed to date employ double-tail or multiple-tail structures for transfection. Single-tail lipidoids are seldom considered for transfection as they have low efficiency in gene delivery. So far, there is no detailed study on the contribution to transfection efficiency of single-tail lipidoids when combined with standard double-tail lipidoids. Here, we use combinatorial chemistry to synthesize 17 double-tail and 17 single-tail lipidoids using thiol-yne and thiol-ene click chemistry, respectively...
January 11, 2016: ACS Combinatorial Science
https://www.readbyqxmd.com/read/26510895/harnessing-dynamic-combinatorial-chemistry-in-the-search-for-new-ligands-for-protein-targets
#18
EDITORIAL
Leticia Monjas, Anna K H Hirsch
No abstract text is available yet for this article.
2015: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/26468125/glutathione-coordinated-2fe-2s-cluster-is-stabilized-by-intramolecular-salt-bridges
#19
Jingwei Li, Stephen A Pearson, Kevin D Fenk, J A Cowan
Halide salts of alkali and alkaline earth metals were used to probe the contributions of intramolecular salt bridge formation on the stability of glutathione-coordinated [2Fe-2S] cluster toward hydrolysis. The effect of ionic strength on cluster stability was quantitatively investigated by application of Debye-Hückel theory to the rates of hydrolysis. Results from this study demonstrate that ionic strength influences the stability of the cluster, with the rate of cluster degradation depending on the charge density, hydrated ionic radius, and hydration energy...
December 2015: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/26384269/late-stage-modification-of-receptors-identified-from-dynamic-combinatorial-libraries
#20
Nicholas K Pinkin, Amanie N Power, Marcey L Waters
Small molecule receptors are attractive potential sensors of post-translational modifications, including methylated lysine and methylated arginine. Using dynamic combinatorial chemistry (DCC), our lab previously identified a suite of receptors that bind to Kme3 with a range of affinities ranging from low micromolar to high nanomolar, each with a unique selectivity for Kme3 over the lower methylation states. To enable these receptors to have broad application as Kme3 sensors, we have developed a method for their late-stage modification, which we used to synthesize biotinylated derivatives of A2B, A2D, and A2G in a single step...
November 28, 2015: Organic & Biomolecular Chemistry
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