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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AG013735-05
Application #
6372065
Study Section
Molecular and Cellular Biophysics Study Section (BBCA)
Program Officer
Snyder, D Stephen
Project Start
1997-04-01
Project End
2003-03-31
Budget Start
2001-04-01
Budget End
2003-03-31
Support Year
5
Fiscal Year
2001
Total Cost
$111,408
Indirect Cost
Name
Boston University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
042250712
City
Boston
State
MA
Country
United States
Zip Code
02215