利用超滤筛选片段混合物文库。
Screening a fragment cocktail library using ultrafiltration.
机构信息
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
出版信息
Anal Bioanal Chem. 2011 Sep;401(5):1585-91. doi: 10.1007/s00216-011-5225-7. Epub 2011 Jul 13.
Abstract
Ultrafiltration provides a generic method to discover ligands for protein drug targets with millimolar to micromolar K(d), the typical range of fragment-based drug discovery. This method was tailored to a 96-well format, and cocktails of fragment-sized molecules, with molecular masses between 150 and 300 Da, were screened against medical structural genomics target proteins. The validity of the method was confirmed through competitive binding assays in the presence of ligands known to bind the target proteins.
摘要
超滤提供了一种通用的方法，用于发现具有毫摩尔至微摩尔 K(d)（片段药物发现的典型范围）的蛋白质药物靶标的配体。该方法针对 96 孔格式进行了定制，并筛选了分子量在 150 至 300 道尔顿之间的片段大小的分子混合物，以针对医学结构基因组学靶蛋白。该方法通过在存在已知与靶蛋白结合的配体的情况下进行竞争结合测定来验证其有效性。
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本文引用的文献
1
Fragment screening by surface plasmon resonance.通过表面等离子体共振进行片段筛选。
ACS Med Chem Lett. 2010 Feb 4;1(1):44-8. doi: 10.1021/ml900002k. eCollection 2010 Apr 8.
2
Immunoaffinity Ultrafiltration with Ion Spray HPLC/MS for Screening Small-Molecule Libraries.用于筛选小分子文库的离子喷雾高效液相色谱/质谱联用免疫亲和超滤法
Anal Chem. 1997 May 1;69(9):1683-91. doi: 10.1021/ac9610265.
3
Fragment-based drug discovery applied to Hsp90. Discovery of two lead series with high ligand efficiency.基于片段的药物发现应用于 Hsp90。发现具有高配体效率的两个先导系列。
J Med Chem. 2010 Aug 26;53(16):5942-55. doi: 10.1021/jm100059d.
4
Subtype-selectivity of metal-dependent methionine aminopeptidase inhibitors.金属依赖性蛋氨酸氨肽酶抑制剂的亚型选择性。
Bioorg Med Chem Lett. 2010 Jul 15;20(14):4038-44. doi: 10.1016/j.bmcl.2010.05.093. Epub 2010 May 27.
5
Drug-protein binding: a critical review of analytical tools.药物-蛋白结合：分析工具的批判性回顾。
Anal Bioanal Chem. 2010 Sep;398(1):53-66. doi: 10.1007/s00216-010-3737-1. Epub 2010 May 9.
6
Catalysis and inhibition of Mycobacterium tuberculosis methionine aminopeptidase.结核分枝杆菌蛋氨酸氨肽酶的催化与抑制。
J Med Chem. 2010 Feb 11;53(3):1329-37. doi: 10.1021/jm901624n.
7
Fragment-based cocktail crystallography by the medical structural genomics of pathogenic protozoa consortium.致病原生动物医学结构基因组学联盟的基于片段的鸡尾酒结晶学。
Curr Top Med Chem. 2009;9(18):1678-87. doi: 10.2174/156802609790102383.
8
Buffer optimization of thermal melt assays of Plasmodium proteins for detection of small-molecule ligands.用于检测小分子配体的疟原虫蛋白质热熔分析的缓冲液优化
J Biomol Screen. 2009 Jul;14(6):700-7. doi: 10.1177/1087057109335749. Epub 2009 May 21.
9
Structural genomics of pathogenic protozoa: an overview.致病原生动物的结构基因组学：概述
Methods Mol Biol. 2008;426:497-513. doi: 10.1007/978-1-60327-058-8_33.
10
A decade of fragment-based drug design: strategic advances and lessons learned.基于片段的药物设计十年：战略进展与经验教训
Nat Rev Drug Discov. 2007 Mar;6(3):211-9. doi: 10.1038/nrd2220. Epub 2007 Feb 9.
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