Related ArticlesNMR Screening and Hit Validation in Fragment Based Drug Discovery.
Curr Top Med Chem. 2010 Sep 2;
Authors: Campos-Olivas R
Over the past three decades nuclear magnetic resonance spectroscopy has been developed into a mature technique for the characterization of interactions of small molecule ligands with their corresponding protein and nucleic acid receptors. In fact, a significant number of industrial and academic laboratories employ NMR for screening small molecule compound collections for binding to defined macromolecular targets, thus potentially providing initial, low affinity hits for a fragment-based approach in the drug discovery process. NMR is also applied to interrogate hits obtained by high throughput screening using biochemical assays and by virtual screening methods, for their ability to physically interact with the target receptor. In favorable cases a variety of NMR-based methods can also provide essential information to validate the hit, rank the different hits according to affinity, and to structurally analyze the ligand-target complex, thus providing essential information for structure-based optimization and medicinal chemistry. In this review a comprehensive overview of the large variety of NMR methods to study interactions between small molecule ligands and macromolecular receptors is provided, summarizing the physico-chemical bases of the different receptor- and ligand-observed experiments. The application of these methods for compound library screening and hit validation, with special emphasis on their contribution to fragment-based drug discovery strategies, is illustrated by recent examples selected from the literature and work in my laboratory.
PMID: 20809889 [PubMed - as supplied by publisher]
Application of NMR and Molecular Docking in Structure-Based Drug Discovery.
Application of NMR and Molecular Docking in Structure-Based Drug Discovery.
Application of NMR and Molecular Docking in Structure-Based Drug Discovery.
Top Curr Chem. 2011 Sep 14;
Authors: Stark JL, Powers R
Abstract
Drug discovery is a complex and costly endeavor, where few drugs that reach the clinical testing phase make it to market. High-throughput screening (HTS) is the primary method used by the pharmaceutical industry to identify initial lead compounds. Unfortunately, HTS has a high failure rate and is not particularly efficient at...
Target immobilization as a strategy for NMR-based fragment screening: comparison of TINS, STD, and SPR for fragment hit identification.
Target immobilization as a strategy for NMR-based fragment screening: comparison of TINS, STD, and SPR for fragment hit identification.
Target immobilization as a strategy for NMR-based fragment screening: comparison of TINS, STD, and SPR for fragment hit identification.
J Biomol Screen. 2010 Sep;15(8):978-89
Authors: Kobayashi M, Retra K, Figaroa F, Hollander JG, Ab E, Heetebrij RJ, Irth H, Siegal G
Fragment-based drug discovery (FBDD) has become a widely accepted tool that is complementary to high-throughput screening (HTS) in developing...
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01-13-2011 12:00 PM
Fragment-based discovery of novel thymidylate synthase leads by NMR screening and group epitope mapping.
Fragment-based discovery of novel thymidylate synthase leads by NMR screening and group epitope mapping.
Fragment-based discovery of novel thymidylate synthase leads by NMR screening and group epitope mapping.
Chem Biol Drug Des. 2010 Sep 1;76(3):218-33
Authors: Begley DW, Zheng S, Varani G
Solution-state nuclear magnetic resonance (NMR) is a versatile tool for the study of binding interactions between small molecules and macromolecular targets. We applied ligand-based NMR techniques to the study of human thymidylate synthase (hTS) using known...
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01-05-2011 09:51 PM
[NMR paper] NMR-based methods and strategies for drug discovery.
NMR-based methods and strategies for drug discovery.
Related Articles NMR-based methods and strategies for drug discovery.
Chem Soc Rev. 2003 Nov;32(6):365-72
Authors: Salvatella X, Giralt E
Nuclear Magnetic Resonance (NMR) spectroscopy has long been a favourite tool of chemists interested in host-guest systems because it permits access to a wealth of information about the molecular recognition reaction. NMR has evolved dramatically in the last 15 years and, in parallel with the development of NMR methods for the determination of protein...
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11-24-2010 09:16 PM
[NMR paper] NMR-based screening methods for lead discovery.
NMR-based screening methods for lead discovery.
Related Articles NMR-based screening methods for lead discovery.
EXS. 2003;(93):183-202
Authors: Vogtherr M, Fiebig K
Diversity and robustness of NMR based screening methods make these techniques highly attractive as tools for drug discovery. Although not all screening techniques discussed here may be applicable to any given target, there is however a good chance that at least one of the described methods will prove productive in finding several medium affinity ligands. A comparison of each of...
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11-24-2010 09:01 PM
[BMNRC community] NMR-based screening: a powerful tool in fragment-based drug discovery
NMR-based screening: a powerful tool in fragment-based drug discovery
http://www.rsc.org/delivery/_ArticleLinking/DisplayHTMLArticleforfree.cfm?JournalCode=AN&Year=2007&ManuscriptID=b709658p&Iss=7
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09-02-2010 04:59 AM
[NMR paper] NMR screening in drug discovery.
NMR screening in drug discovery.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles NMR screening in drug discovery.
Curr Opin Biotechnol. 1999 Feb;10(1):54-8
Authors: Moore JM
NMR methods in drug discovery have traditionally been used to obtain structural information for drug targets or target-ligand complexes. Recently, it has been shown that NMR may be used as an alternative approach for identification of ligands that bind to protein drug targets, shifting the emphasis...
NMR Screening and Hit Validation in Fragment Based Drug Discovery.
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