Substoichiometric inhibition of Abeta(1-40) aggregation by a tandem Abeta(40-1-Gly8-1-40) peptide.
Abeta peptides aggregate to form insoluble and neurotoxic fibrils associated with Alzheimer's disease. Inhibition of the aggregation has been the subject of numerous studies. Here we describe a novel, substoichiometric inhibitor of Abeta(1-40) fibrillization as a tandem dimeric construct consisting of Abeta(40-1) (reverse sequence) linked to Abeta(1-40) via an eight residue glycine linker. At molar ratios of the tandem peptide to Abeta(1-40) of 1:10 to 1:25 inhibition of fibrillization, as measured by ThioflavinT, was observed. We postulate that the tandem construct binds to a fibrillar intermediate but the reverse sequence delays or prevents further monomer association.
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA.
Sourajit M
SM
Mustafi
Kanchan
K
Garai
Scott L
SL
Crick
Berevan
B
Baban
Carl
C
Frieden
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D052160:Benzothiazoles; D002942:Circular Dichroism; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D018625:Microscopy, Atomic Force; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D013844:Thiazoles / Q000737:chemistry
D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D005456:Fluorescent Dyes; D010446:Peptide Fragments; D010455:Peptides; D013844:Thiazoles; C078592:amyloid beta-protein (1-40); C551407:amyloid-beta(40-1)-Gly8-1-40 peptide; C009462:thioflavin T