Related ArticlesNMR fragment screening: tackling protein-protein interaction targets.
Curr Opin Drug Discov Devel. 2005 May;8(3):365-73
Authors: Schade M, Oschkinat H
High-throughput screening of libraries containing compounds of 'drug-like' molecular weight has frequently resulted in no or poor drug candidates, especially when screening against demanding drug targets such as protein-protein interactions. Fragment-based lead discovery and optimization has evolved as a promising solution to this problem by combining the universal adaptability of low-molecular-weight fragments with immediate structural information on fragment binding modes. This review focuses on nuclear magnetic resonance (NMR) fragment screening techniques, which provide a unique combination of medium-throughput, direct binding site information and broad applicability. The utility and exemplary data of chemical shift-detected NMR fragment screening applied to the challenging protein-protein interaction target PDZ domains are summarized.
An NMR strategy for fragment-based ligand screening utilizing a paramagnetic lanthanide probe.
An NMR strategy for fragment-based ligand screening utilizing a paramagnetic lanthanide probe.
An NMR strategy for fragment-based ligand screening utilizing a paramagnetic lanthanide probe.
J Biomol NMR. 2011 Sep 17;
Authors: Saio T, Ogura K, Shimizu K, Yokochi M, Burke TR, Inagaki F
Abstract
A nuclear magnetic resonance-based ligand screening strategy utilizing a paramagnetic lanthanide probe is presented. By fixing a paramagnetic lanthanide ion to a target protein, a pseudo-contact shift (PCS) and a paramagnetic relaxation...
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09-20-2011 03:10 PM
An NMR strategy for fragment-based ligand screening utilizing a paramagnetic lanthanide probe
An NMR strategy for fragment-based ligand screening utilizing a paramagnetic lanthanide probe
Abstract A nuclear magnetic resonance-based ligand screening strategy utilizing a paramagnetic lanthanide probe is presented. By fixing a paramagnetic lanthanide ion to a target protein, a pseudo-contact shift (PCS) and a paramagnetic relaxation enhancement (PRE) can be observed for both the target protein and its bound ligand. Based on PRE and PCS information, the bound ligand is then screened from the compound library and the structure of the ligandâ??protein complex is determined. PRE is an...
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09-20-2011 05:02 AM
Cracking the molecular weight barrier: Fragment screening of an aminotransferase using an NMR-based functional assay.
Cracking the molecular weight barrier: Fragment screening of an aminotransferase using an NMR-based functional assay.
Cracking the molecular weight barrier: Fragment screening of an aminotransferase using an NMR-based functional assay.
Bioorg Med Chem Lett. 2011 Jul 21;
Authors: Mendoza R, Petros AM, Liu Y, Thimmapaya R, Surowy CS, Leise WF, Pereda-Lopez A, Panchal SC, Sun C
NMR-based screening of protein targets has become a well established part of the drug discovery process especially with respect to fragments. However, as target size increases...
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08-16-2011 01:19 PM
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
[NMR paper] Druggability indices for protein targets derived from NMR-based screening data.
Druggability indices for protein targets derived from NMR-based screening data.
Related Articles Druggability indices for protein targets derived from NMR-based screening data.
J Med Chem. 2005 Apr 7;48(7):2518-25
Authors: Hajduk PJ, Huth JR, Fesik SW
An analysis of heteronuclear-NMR-based screening data is used to derive relationships between the ability of small molecules to bind to a protein and various parameters that describe the protein binding site. It is found that a simple model including terms for polar and apolar surface area,...
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11-25-2010 08:21 PM
[NMR paper] Expression screening, protein purification and NMR analysis of human protein domains
Expression screening, protein purification and NMR analysis of human protein domains for structural genomics.
Related Articles Expression screening, protein purification and NMR analysis of human protein domains for structural genomics.
J Struct Funct Genomics. 2004;5(1-2):119-31
Authors: Folkers GE, van Buuren BN, Kaptein R
Structural genomics, the determination of protein structures on a genome-wide scale, is still in its infancy for eukaryotes due to the number and size of their genes. Low protein expression and solubility of eukaryotic...
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11-24-2010 09:25 PM
[NMR paper] High-throughput screening of structural proteomics targets using NMR.
High-throughput screening of structural proteomics targets using NMR.
Related Articles High-throughput screening of structural proteomics targets using NMR.
FEBS Lett. 2003 Sep 25;552(2-3):207-13
Authors: Galvão-Botton LM, Katsuyama AM, Guzzo CR, Almeida FC, Farah CS, Valente AP
We applied a high-throughput strategy for the screening of targets for structural proteomics of Xanthomonas axonopodis pv citri. This strategy is based on the rapid (1)H-(15)N HSQC NMR analysis of bacterial lysates containing selectively (15)N-labelled heterologous...
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11-24-2010 09:16 PM
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...
NMR fragment screening: tackling protein-protein interaction targets.
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