Multiple N-methylation by a designed approach enhances receptor selectivity

被引：65

作者：

Chatterjee, Jayanta

Ovadia, Oded

Zahn, Grit

Marinelli, Luciana

Hoffman, Amnon

Gilon, Chaim

Kessler, Horst

机构：

[1] Tech Univ Munich, Lehrstuhl Organ Chem 2, Ctr Integrated Protein Sci, D-85747 Garching, Germany

[2] Hebrew Univ Jerusalem, Dept Pharmaceut, IL-91904 Jerusalem, Israel

[3] Hebrew Univ Jerusalem, Dept Organ Chem, IL-91904 Jerusalem, Israel

[4] Jerini AG, D-10115 Berlin, Germany

[5] Univ Naples Federico 2, I-80131 Naples, Italy

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2007年 / 50卷 / 24期

关键词：

D O I：

10.1021/jm701044r

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：5878 / 5881

页数：4

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