Stereochemical effects of all-hydrocarbon tethers in i,i+4 stapled peptides

被引：67

作者：

Kim, Young-Woo ^{[1
,3
]}

Verdine, Gregory L. ^{[1
,2
,3
]}

机构：

[1] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA

[2] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA

[3] Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 09期

关键词：

Stapled peptides; alpha-Helix; Stereochemical effects; Helicity; Cellular uptake mechanism; BH3; HELIX;

D O I：

10.1016/j.bmcl.2009.03.022

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The stereochemical effects of the hydrocarbon crosslink on the conformation and cellular uptake of i,i+4 stapled peptides were studied. Compared to its S, S-configurated counterpart, the crosslink bearing the R,R-configuration provided a significantly diminished helix stabilizing effect and conferred less efficient cellular uptake on the stapled peptides. These results suggest that the vesicular trafficking pathway employed by cells to take up stapled peptides is sensitive to the extent of helical character in the peptide, with greater helicity conferring increased cellular uptake. (C) 2009 Elsevier Ltd. All rights reserved.

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页码：2533 / 2536

页数：4

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