Poster Session I Abstracts

Abstract

Peptide self-assembly processes are central to the etiology of amyloid diseases. Much effort has been devoted to characterizing amyloid structure and the mechanisms of peptide self-assembly leading to amyloid. The application of unnatural biopolymers for the selective inhibition of helical protein-protein interactions is an interesting strategy for drug discovery. Peptides composed of homologous amino acids at present are among the most widely studied biopolymers and their enormous potential for secondary [1] and quaternary [2] structure is already known. Theoretical studies (ab initio MO theory) have shown that hybrid peptides composed of alternatingand -amino acids are well suited to mimic -helical conformation [3], and our results support experimentally this idea [4]. To generate the chimera B32, the two central turns of the helix in a basic model -peptide (Base-pp) were replaced by a pentad of alternatingand -amino acids. Heteromeric coiled-coil formation between B32 and the -peptide (Acid-pp) was proven by a combination of analytical methods. Our data provide strong evidence for the specific contribution ofandamino acid side chains to the stability of the chimeric helical folding motif.