l-Ala Modified Analogues of Amyloid β-Peptide Residue 17-20: Self-Association and Amyloid-like Fibril Formation

• Published in: International journal of peptide research and therapeutics Vol. 12; no. 4; pp. 341 - 348
• Main Authors: Haldar, Debasish, Banerjee, Arindam
• Format: Journal Article
• Language: English
• Published: 01.12.2006
• ISSN: 1573-3149; 1573-3904
• DOI: 10.1007/s10989-006-9037-0

l-Ala modified analogues of amyloid beta -peptide residue 17-20 LVFF (-l-Leu-l-Val-l-Phe-l-Phe-) have been designed and synthesized to study their self-assembling propensity, the nature of intermolecular interactions and rationalize with short hydrophobic sequences in the middle of A beta that have important role in the neuropathology of Alzheimer's disease. The peptides sequences LVFA and LAFA have been adopted from the beta -sheet region of non-amyloidogenic proteins (hemoglobin-like falvoprotein and ATP synthase C chain, respectively). All the reported peptides self-associate into amyloid-like fibrils which are readily stained with a physiological dye Congo red and exhibits green gold birefringence under polarized light. The solid state FTIR studies of the fibrils reveal that the reported peptides self-associate through intermolecular hydrogen bonds to form antiparallel beta -sheet structure, which is also supported by molecular modeling studies. This result suggests that l-Ala analogous of A beta 17-20, LVFA and LAFA also have virtually identical aggregation behavior.