Identification and assessment of novel targets is essential to combat drug resistance in the treatment of HIV/AIDS. HIV Capsid (HIV-CA), the protein playing a major role in both the early and late stages of the viral life cycle, has emerged as an important target. We have applied an NMR fragment screening platform and identified molecules that bind to the N-terminal domain (NTD) of HIV-CA at a site close to the interface with the C-terminal domain (CTD). Using X-ray crystallography, we have been...
Efficiently driving protein-based fragment screening and lead discovery using two-dimensional NMR
Efficiently driving protein-based fragment screening and lead discovery using two-dimensional NMR
Abstract
Fragment-based drug discovery (FBDD) and validation of small molecule binders using NMR spectroscopy is an established and widely used method in the early stages of drug discovery. Starting from a library of small compounds, ligand- or protein-observed NMR methods are employed to detect binders, typically weak, that become the starting points for structureâ??activity relationships (SAR) by NMR. Unlike the more frequently used ligand-observed 1D...
[NMR paper] Protein-observed (19)F-NMR for fragment screening, affinity quantification and druggability assessment.
Protein-observed (19)F-NMR for fragment screening, affinity quantification and druggability assessment.
Protein-observed (19)F-NMR for fragment screening, affinity quantification and druggability assessment.
Nat Protoc. 2016 Aug;11(8):1414-27
Authors: Gee CT, Arntson KE, Urick AK, Mishra NK, Hawk LM, Wisniewski AJ, Pomerantz WC
Abstract
NMR spectroscopy can be used to quantify the binding affinity between proteins and low-complexity molecules, termed 'fragments'; this versatile screening approach allows researchers to assess the...
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07-16-2016 04:54 AM
[NMR paper] NMR-based platform for fragment-based lead discovery used in screening BRD4-targeted compounds.
NMR-based platform for fragment-based lead discovery used in screening BRD4-targeted compounds.
http://www.bionmr.com//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www.nature.com-images-lo_npg.gif Related Articles NMR-based platform for fragment-based lead discovery used in screening BRD4-targeted compounds.
Acta Pharmacol Sin. 2016 May 30;
Authors: Yu JL, Chen TT, Zhou C, Lian FL, Tang XL, Wen Y, Shen JK, Xu YC, Xiong B, Zhang NX
Abstract
AIM: Fragment-based lead discovery (FBLD) is a complementary approach in drug...
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05-31-2016 09:07 PM
[NMR paper] Fragment Screening and Druggability Assessment for the CBP/p300 KIX Domain through Protein-Observed (19) F NMR Spectroscopy.
Fragment Screening and Druggability Assessment for the CBP/p300 KIX Domain through Protein-Observed (19) F NMR Spectroscopy.
Fragment Screening and Druggability Assessment for the CBP/p300 KIX Domain through Protein-Observed (19) F NMR Spectroscopy.
Angew Chem Int Ed Engl. 2015 Feb 4;
Authors: Gee CT, Koleski EJ, Pomerantz WC
Abstract
(19) F NMR spectroscopy of labeled proteins is a sensitive method for characterizing structure, conformational dynamics, higher-order assembly, and ligand binding. Fluorination of aromatic side...
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02-05-2015 12:00 PM
[NMR paper] Comparing Binding Modes of Analogous Fragments Using NMR in Fragment-Based Drug Design: Application to PRDX5.
Comparing Binding Modes of Analogous Fragments Using NMR in Fragment-Based Drug Design: Application to PRDX5.
Comparing Binding Modes of Analogous Fragments Using NMR in Fragment-Based Drug Design: Application to PRDX5.
PLoS One. 2014;9(7):e102300
Authors: Aguirre C, Brink TT, Guichou JF, Cala O, Krimm I
Abstract
Fragment-based drug design is one of the most promising approaches for discovering novel and potent inhibitors against therapeutic targets. The first step of the process consists of identifying fragments that bind...
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07-16-2014 10:46 AM
NMR Screening and Hit Validation in Fragment Based Drug Discovery.
NMR Screening and Hit Validation in Fragment Based Drug Discovery.
Related Articles NMR 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...
Application of an NMR/crystallography fragment screening platform for the assessment and rapid discovery of new HIV-CA binding fragments
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