Effect of acid predissolution on fibril size and fibril flexibility of synthetic beta-amyloid peptide.
beta-amyloid peptide (A beta) is the major protein component of senile plaques and cerebrovascular amyloid deposits in Alzheimer's patients. Several researchers have demonstrated that A beta is neurotoxic in in vitro and in vivo systems. Peptide aggregation state and/or conformation might play a significant role in determining the toxicity of the peptide. The size and flexibility of fibrils formed from the synthetic peptide beta (1-39), corresponding to the first 39 residues of A beta, were determined. Samples were prepared either directly from lyophilized peptide or diluted from a 10 mg/ml stock solution in 0.1% trifluoroacetic acid (TFA). All samples had a final peptide concentration of 0.5 mg/ml, a final pH of 7.4, and a final NaCl concentration of 0.14 M. The molecular weight and linear density of the fibrils increased with increasing pre-incubation time in TFA, based on static light scattering measurements. Analysis of the angular dependence of the intensity of scattered light indicated that the fibrils were semi-flexible chains and that the fibril flexibility decreased with increasing pre-incubation time in TFA. There was a concomitant change in phase behavior from precipitation to gelation with the decrease in fibril flexibility.
Shen
C L
CL
Department of Chemical Engineering, University of Wisconsin, Madison 53706.
Fitzgerald
M C
MC
Murphy
R M
RM
D000544:Alzheimer Disease / Q000378:metabolism; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification; D055592:Biophysical Phenomena; D001703:Biophysics; D011232:Chemical Precipitation; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D006801:Humans; D066298:In Vitro Techniques; D008027:Light; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012542:Scattering, Radiation; D012995:Solubility; D014269:Trifluoroacetic Acid
D016229:Amyloid beta-Peptides; D014269:Trifluoroacetic Acid