基于结构的药物设计中的柱上配体交换：以人11β-羟基类固醇脱氢酶1型为例的研究
On-column ligand exchange for structure-based drug design: a case study with human 11β-hydroxysteroid dehydrogenase type 1.
作者信息
Qin Wenying, Judge Russell A, Longenecker Kenton L, Solomon Larry R, Harlan John E
机构信息
Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA.
出版信息
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 May 1;68(Pt 5):601-5. doi: 10.1107/S1744309112010172. Epub 2012 Apr 21.
Abstract
Successfully forming ligand-protein complexes with specific compounds can be a significant challenge in supporting structure-based drug design for a given protein target. In this respect, an on-column ligand- and detergent-exchange method was developed to obtain ligand-protein complexes of an adamantane series of compounds with 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) after a variety of other complexation methods had failed. This report describes the on-column exchange method and an unexpected byproduct of the method in which artificial trimers were observed in the structures.
摘要
对于给定的蛋白质靶点，成功地与特定化合物形成配体 - 蛋白质复合物可能是基于结构的药物设计面临的一项重大挑战。在这方面，在多种其他络合方法均失败后，开发了一种柱上配体和去污剂交换方法，以获得金刚烷系列化合物与11β - 羟基类固醇脱氢酶1型（11β - HSD1）的配体 - 蛋白质复合物。本报告描述了柱上交换方法以及该方法中一个意外的副产物，即在结构中观察到了人工三聚体。
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