Construction of peptides that undergo structural transition from α-helix to β-sheet and amyloid fibril formation by the introduction of N-terminal hydrophobic amino acids

Recent studies on amyloid disease-related proteins such as beta-amyloid and prion have pointed out that conformational alternation and subsequent aggregation to form amyloid fibrils play a key role in such fatal diseases. Here, design and synthesis of peptides undergoing a structural transition from alpha-helix to beta-sheet and self-assembly into amyloid fibrils are described. A dimeric peptide was designed to form a coiled-coil alpha-helix structure and the N-terminus was modified with various kinds of standard hydrophobic amino acids. The self-initiated structural transition to beta-sheet was induced by appropriate hydrophobic amino acids attached to the N-termini of the peptides. Moreover, the peptides in beta-sheet self-assembled into the amyloid with a well-organized fibrilar structure. Simplified model peptides like those presented here will lead to a better understanding of the process by which conformational alternation and aggregation of proteins occur, as well as to developing novel nanoscale materials. (C) 2000 Elsevier Science Ltd. All rights reserved.