阿尔茨海默病药物的潜在线索：一种能阻断分子间相互作用及淀粉样β蛋白诱导的细胞毒性的肽。

Potential lead for an Alzheimer drug: a peptide that blocks intermolecular interaction and amyloid beta protein-induced cytotoxicity.

作者信息

Kwak Ju-Won, Kim Hyun-Kyung, Chae Chi-Bom

机构信息

Division of Molecular and Life Sciences, Postech Biotech Center, Pohang University of Science and Technology, San31 Hyoja-dong, Pohang, Kyungbuk 790-784, Republic of Korea.

出版信息

J Med Chem. 2006 Aug 10;49(16):4813-7. doi: 10.1021/jm050718v.

DOI:10.1021/jm050718v

PMID:16884292

Abstract

A peptide chAbeta30-16 (15-mer; CTFVRTHIFCKEHQF) was designed to bind to a region encompassing the entire polymerization-related (16KLVFF20) and part of the polymerization and toxicity-related (25GSNKGAIIGLM35) regions of amyloid beta-protein, Abeta1-42 by a hydropathic complementary approach. This peptide efficiently binds to Abeta and blocks intermolecular interaction and the formation of Abeta aggregates. In addition, the peptide neutralizes the cell toxicity of Abeta fibrils. The chAbeta30-16 peptide or its derivatives may be a starting point for the future development of drugs that prevent the neurotoxicity and deposition of Abeta in the brain of Alzheimer's disease.

摘要

一种肽chAbeta30 - 16（15肽；CTFVRTHIFCKEHQF）通过亲水性互补方法设计，以结合包含淀粉样β蛋白（Aβ1 - 42）整个聚合相关区域（16KLVFF20）以及部分聚合和毒性相关区域（25GSNKGAIIGLM35）的区域。该肽能有效结合Aβ并阻断分子间相互作用以及Aβ聚集体的形成。此外，该肽可中和Aβ纤维的细胞毒性。chAbeta30 - 16肽或其衍生物可能是未来开发预防阿尔茨海默病大脑中Aβ神经毒性和沉积药物的起点。