ENERGETICS/FOLDING/AMYLOIDOGENESIS--ALZHEIMERS DISEASE

Boston University, Boston MA

Investigators

Linked publications & trials

Abstract

DESCRIPTION: The major focus of this proposal is characterization of the solution conformations of peptides derived from the A-beta protein found in the amyloid plaques associated with Alzheimer's disease. In previous work, Dr. Lee, in collaboration with Dr. John Maggio, has identified a soluble peptide fragment that is both amenable to NMR studies and displays activity in an in vitro plaque-growth assay. He has already determined a solution structure for this fragment and has made 15N relaxation measurements of selected backbone amide groups. In addition, he has found evidence for a pH-dependent conformational change. By studying both the solution conformation and activities of a series of sequence variants, Dr. Lee hopes to establish correlations between conformation and plaque formation. He also plans to carry out detailed molecular dynamics simulations, in collaboration with Dr. John Straub.