Multiple N-methylation by a designed approach enhances receptor selectivity
Multiple N-methylation by a designed approach enhances receptor selectivity
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DOI：
10.1021/jm701044r
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发表时间：
2007-11-29
影响因子：
7.3
通讯作者：
Kessler, Horst
中科院分区：
文献类型：
--
作者：
Chatterjee, Jayanta;Ovadia, Oded;Kessler, Horst
通过设计的方法将非选择性环肽整联蛋白配体依次N-甲基化，其中仅外部取向的（溶剂暴露的）酰胺键被N-甲基化。N-甲基化导致不同整合素受体亚型（α 5 β 1、α v β 3和α IIb β 3）之间的选择性极大增强。进行了构象和对接研究，表明受体选择性主要是由N-甲基化导致的骨架柔性降低引起的。
An unselective cyclic peptide integrin ligand was sequentially N-methylated by a designed approach, where only the externally oriented (solvent exposed) amide bonds were N-methylated. The N-methylation resulted in tremendous enhancement in selectivity among the different integrin receptor subtypes (alpha 5 beta 1, alpha v beta 3, and alpha IIb beta 3). Conformational and docking studies were performed, which suggested that the receptor selectivity is principally caused by reduced backbone flexibility due to N-methylation.