ORGN 518 |
| Terpene trilactones (TTLs), ginkgolides (I) and bilobalide (II), from Ginkgo biloba extract are the main active ingredients that are responsible for a variety of neuromodulatory actions attributed to the extract. Recent studies from ours and other labs have shown that TTLs 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 the Ginkgo biloba extract and TTLs action on these peptides remains largely unknown. We have carried out a series of chromatographic and spectroscopic experiments, aimed at establishing the direct effect of TTLs on the time-dependent behavior of several b-amyloid peptides, (Ab(16-22), Ab(10-35) and Ab(1-42)) under a variety of conditions. Native TTLs 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 of TTLs via functionalization of hydroxyl groups of TTLs (III) as well as by modification of ginkgolide skeleton (IV). Preparation of these compounds and their effect on the aggregation of the amyloid peptides will be discussed.
|
|
Proteins, Peptides, Amino Acids, and Enzyme Inhibitors
8:00 AM-11:40 AM, Wednesday, 31 August 2005 Washington DC Convention Center -- 202B, Oral
Division of Organic Chemistry |
