'Click' assembly of glycoclusters and discovery of a trehalose analogue that retards Aβ40 aggregation and inhibits Aβ40-induced neurotoxicity

被引：26

作者：

Rajaram, Hemalatha ^{[1
]}

Palanivelu, Manoj Kumar ^{[1
]}

Arumugam, Thiruma V. ^{[2
]}

Rao, Venkatesan M. ^{[1
]}

Shaw, P. Nicholas ^{[1
]}

McGeary, Ross P. ^{[3
]}

Ross, Benjamin P. ^{[1
]}

机构：

[1] Univ Queensland, Sch Pharm, Brisbane, Qld 4072, Australia

[2] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Physiol, Singapore 117597, Singapore

[3] Univ Queensland, Sch Chem & Mol Biosci, Brisbane, Qld 4072, Australia

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 18期

关键词：

Alzheimer's disease; Amyloid beta-peptides; Click chemistry; Glycoclusters; Osmolytes; AMYLOID-BETA-PROTEIN; CIRCULAR-DICHROISM SPECTROSCOPY; SECONDARY STRUCTURE; ALZHEIMERS-DISEASE; PRECURSOR PROTEIN; PEPTIDE; STABILIZATION; MECHANISM; PREVENTS; PHASE;

D O I：

10.1016/j.bmcl.2014.07.077

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Osmolytes have been proposed as treatments for neurodegenerative proteinopathies including Alzheimer's disease. However, for osmolytes to reach the clinic their efficacy must be improved. In this work, copper(I)-catalyzed azide-alkyne cycloaddition chemistry was used to synthesize glycoclusters bearing six copies of trehalose, lactose, galactose or glucose, with the aim of improving the potency of these osmolytes via multivalency. A trehalose glycocluster was found to be superior to monomeric trehalose in its ability to retard the formation of amyloid-beta peptide 40 (A beta 40) fibrils and protect neurons from A beta 40-induced cell death. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：4523 / 4528

页数：6

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