Synthesis of scyllo-inositol derivatives and their effects on amyloid beta peptide aggregation

被引：56

作者：

Sun, Yedi ^{[1
]}

Zhang, Guohua ^{[1
]}

Hawkes, Cheryl A. ^{[2
,3
]}

Shaw, James E. ^{[2
,3
]}

McLaurin, JoAnne ^{[2
,3
]}

Nitz, Mark ^{[1
]}

机构：

[1] Univ Toronto, Dept Chem, Toronto, ON M5S 3H6, Canada

[2] Univ Toronto, Ctr Res Neurodegenerat Dis, Toronto, ON M5S 3H6, Canada

[3] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 3H6, Canada

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 15期

基金：

加拿大健康研究院;

关键词：

scyllo-inositol; Alzheimer's; amyloid; inositol; A beta peptide; aggregation inhibitors;

D O I：

10.1016/j.bmc.2008.06.045

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

scyllo-Inositol has shown promise as a potential therapeutic for Alzheimer's disease, by directly interacting with the amyloid beta (A beta) peptide to inhibit A beta 42. ber formation. To explore the molecular details of the inositol-A beta 42 interaction, a series of scyllo-inositol derivatives have been synthesized which contain deoxy, fluoro, chloro, and methoxy substitutions. The effects of these compounds on the aggregation cascade of A beta 42 have been investigated using electron microscopy (EM). EM analyses revealed that the 1-deoxy- 1-fluoro-and 1,4-dimethyl-scyllo-inositols significantly inhibit the formation of A beta 42 fibers. The other derivatives showed some alterations in the morphology of the A beta 42 fibers produced. These findings indicate the importance of all of the hydroxyl groups of scyllo-inositol for complete inhibition of A beta aggregation. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：7177 / 7184

页数：8

共 26 条

[1]

CYCLITOLS .38. THE PREPARATION OF CYCLOHEXANEPENTOLS FROM INOSITOLS BY DEOXYGENATION [J].