application) The core laboratory provides chemical synthesis, purification, and analysis services to each of the projects. By centralizing these activities, the project will make more efficient use of its resources and insure high quality and consistency in the starting materials for each section. Specifically, the core will synthesize wild type amyloid beta-proteins, truncated and elongated forms, as well as derivatives containing amino acid substitutions, D-isomers, unusual amino acids, and radioactive and stable atomic isomers. Peptide and non-peptide inhibitors of fibrillogenesis will be prepared. Cleaved and deprotected peptides will be purified (greater than 95%+) by HPLC to ensure homogeneous starting material. Chemical and isotopic purity will be confirmed by analytical HPLC, amino acid analysis, protein sequencing, and mass spectrometry. Proteins produced in in vitro expression systems will be purified and characterized by similar means.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
1P01AG014366-02
Application #
6267700
Study Section
Project Start
1998-07-15
Project End
1999-05-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115
Yong, Winnie; Lomakin, Aleksey; Kirkitadze, Marina D et al. (2002) Structure determination of micelle-like intermediates in amyloid beta -protein fibril assembly by using small angle neutron scattering. Proc Natl Acad Sci U S A 99:150-4
Astrof, Nathan S; Griffin, Robert G (2002) Soft-triple resonance solid-state NMR experiments for assignments of U-13C, 15N labeled peptides and proteins. J Magn Reson 158:157-63
Fezoui, Youcef; Teplow, David B (2002) Kinetic studies of amyloid beta-protein fibril assembly. Differential effects of alpha-helix stabilization. J Biol Chem 277:36948-54
Astrof, N S; Lyon, C E; Griffin, R G (2001) Triple resonance solid state NMR experiments with reduced dimensionality evolution periods. J Magn Reson 152:303-7
Fezoui, Y; Hartley, D M; Harper, J D et al. (2000) An improved method of preparing the amyloid beta-protein for fibrillogenesis and neurotoxicity experiments. Amyloid 7:166-78
Walsh, D M; Hartley, D M; Kusumoto, Y et al. (1999) Amyloid beta-protein fibrillogenesis. Structure and biological activity of protofibrillar intermediates. J Biol Chem 274:25945-52
Harper, J D; Wong, S S; Lieber, C M et al. (1999) Assembly of A beta amyloid protofibrils: an in vitro model for a possible early event in Alzheimer's disease. Biochemistry 38:8972-80
Lomakin, A; Benedek, G B; Teplow, D B (1999) Monitoring protein assembly using quasielastic light scattering spectroscopy. Methods Enzymol 309:429-59
Watson, D J; Selkoe, D J; Teplow, D B (1999) Effects of the amyloid precursor protein Glu693-->Gln 'Dutch' mutation on the production and stability of amyloid beta-protein. Biochem J 340 ( Pt 3):703-9
Teplow, D B (1998) Structural and kinetic features of amyloid beta-protein fibrillogenesis. Amyloid 5:121-42

Showing the most recent 10 out of 13 publications