Synthesis of scyllo-inositol derivatives and their effects on amyloid beta peptide aggregation.
scyllo-Inositol has shown promise as a potential therapeutic for Alzheimer's disease, by directly interacting with the amyloid beta (Abeta) peptide to inhibit Abeta42 fiber formation. To explore the molecular details of the inositol-Abeta42 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 Abeta42 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 Abeta42 fibers. The other derivatives showed some alterations in the morphology of the Abeta42 fibers produced. These findings indicate the importance of all of the hydroxyl groups of scyllo-inositol for complete inhibition of Abeta aggregation.
Sun
Yedi
Y
Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ont., Canada M5S 3H6.
Zhang
Guohua
G
Hawkes
Cheryl A
CA
Shaw
James E
JE
McLaurin
JoAnne
J
Nitz
Mark
M
D000544:Alzheimer Disease; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D002236:Carbohydrate Conformation; D007294:Inositol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D007294:Inositol