Chatterjee Jayanta, Ovadia Oded, Zahn Grit, Marinelli Luciana, Hoffman Amnon, Gilon Chaim, Kessler Horst
Center for Integrated Protein Science at the Department Chemie, Lehrstuhl II für Organische Chemie, Technische Universität München, Lichtenbergstrasse 4, Garching D85747, Germany.
J Med Chem. 2007 Nov 29;50(24):5878-81. doi: 10.1021/jm701044r. Epub 2007 Nov 1.
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 (alpha5beta1, alphavbeta3, and alphaIIbbeta3). Conformational and docking studies were performed, which suggested that the receptor selectivity is principally caused by reduced backbone flexibility due to N-methylation.
一种非选择性环肽整合素配体通过一种设计方法进行顺序N-甲基化，其中仅对外向（溶剂暴露）的酰胺键进行N-甲基化。N-甲基化导致不同整合素受体亚型（α5β1、αvβ3和αIIbβ3）之间的选择性大幅提高。进行了构象和对接研究，结果表明受体选择性主要是由于N-甲基化导致主链灵活性降低所致。
