On-column ligand exchange for structure-based drug design: a case study with human 11β-hydroxysteroid dehydrogenase type 1

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

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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.

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