AEI: Modulation of b-amyloid peptides self-assembly by ginkgolides

ORGN 433

Sergei V. Dzyuba, svd212@columbia.edu1, Yan Liang, yliang2@emory.edu2, Rong Ni2, David G. Lynn, dlynn2@emory.edu2, Nina D. Berova, ndb1@columbia.edu1, and Koji Nakanishi, kn5@columbia.edu1. (1) Department of Chemistry, Columbia University, 3000 Broadway, New York, NY 10027, (2) Departments of Chemistry and Biology, Emory University, 1515 Dickey Drive, Atlanta, GA 30322
Ginkgolides (I) are one of the main active ingredients of Ginkgo biloba extract that are responsible for a variety of neuromodulatory actions attributed to the extract. Recent studies from ours and other labs have shown that ginkgolides can also suppress the neurotoxicity of b-amyloid peptides that are believed to be the major species involved in the occurrence and progression of Alzheimer's disease. However, the mechanism of Ginkgo biloba extract and TTLs action on these peptides remains largely unknown. We carried out a series of chromatographic and spectroscopic experiments, aimed at establishing the direct effect of ginkgolides on the time-dependent behavior of several amyloid peptides, such as Ab(16-22), Ab(10-35) and Ab(1-42), under a variety of conditions. All of the native ginkgolides had some effect on the early stages of peptide aggregation as well as the overall thermodynamics of self-assembly. In order to probe the structural features that are responsible for these interactions, we have synthesized several derivatives via functionalization of hydroxyl groups of (II) as well as by modification of ginkgolide skeleton (III). Preparation of these compounds and their effect on the aggregation of amyloid peptides will be presented.

 

Sci-Mix
8:00 PM-10:00 PM, Monday, 29 August 2005 Washington DC Convention Center -- Hall A, Sci-Mix

Division of Organic Chemistry

The 230th ACS National Meeting, in Washington, DC, Aug 28-Sept 1, 2005