Aromatic Versus Hydrophobic Contributions to Amyloid Peptide Self-Assembly

摘要

Peptide self-assembly processes are central to the etiology of amyloid diseases [1]. Much effort has been devoted to characterizing amyloid structure and the mechanisms of peptide selfassembly leading to amyloid. It has been proposed that aromatic n-n interactions play a central role in early self-assembly recognition events [2], but this contention remains somewhat controversial [3]. Recent studies have indicated that in some amyloid peptides, including the islet amyloid polypeptide (IAPP), aromatic residues can be exchanged for other hydrophobic residues and these non-aromatic variant peptides still retain competency to form amyloid, although with attenuated kinetics [3]. In an effort to understand the relative contributions of aromatic versus generic hydrophobic interactions, studies to quantify the self-assembly properties of amyloid peptides as a function of increasing hydrophobicity and altered aromatic character have been undertaken. Model peptides have been chosen in which at least one aromatic side-chain is present; the focus of this abstract is the amphipathic (FKFE)2 peptide [4]. The aromatic residues have been systematically replaced with natural and nonnatural residues with varying hydrophobicity and aromaticity and the self-assembly properties have been characterized [5]. These studies confirm that aromatic interactions are not strictly required for amyloid formation.