'Nature-inspired' drug-protein complexes as inhibitors of Aβ aggregation

被引：17

作者：

Bose, M ^{[1
]}

Gestwicki, JE ^{[1
]}

Devasthali, V ^{[1
]}

Crabtree, GR ^{[1
]}

Graef, IA ^{[1
]}

机构：

[1] Stanford Univ, Howard Hughes Med Inst, Sch Med, Dept Pathol, Stanford, CA 94305 USA

来源：

BIOCHEMICAL SOCIETY TRANSACTIONS | 2005年 / 33卷

关键词：

aggregation; amyloid beta; chaperone; FK506-binding protein; linker; small-molecule ligand;

D O I：

10.1042/BST0330543

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Protein-protein interactions are a regulatory mechanism for a number of physiological and pathological cellular processes. Neurodegenerative diseases, such as AD (Alzheimer's disease), are associated with the accelerated production or delayed clearance of protein aggregates. Hence, inhibition of pathologic protein-protein interactions is a very attractive mechanism for drug development. This review focuses on a novel therapeutic strategy to inhibit the de novo formation of protein aggregates. Inspired by strategies used in Nature and optimized over millions of years of evolution, we have created a bifunctional molecule [SLF (synthetic ligand for FK506-binding protein)-CR (Congo Red)] that is able to block A beta (amyloid beta) aggregation by borrowing the surface and steric bulk of a cellular chaperone.

引用

页码：543 / 547

页数：5

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