Effects of copolypeptides on amyloid fibrillation of hen egg‐white lysozyme

Abstract

The fibrillation of hen egg-white lysozyme (HEWL) in the absence and presence of simple, unstructured D,L-lysine-co-glycine (D,L-Lys-co-gly) and D,L-lysine-co-L-phenylalanine (D,L-Lys-co-Phe) copolypeptides was studied by using a variety of analytical techniques. The attenuating and decelerating effects on fibrillation are significantly dependent on the polypeptide concentration and the composition ratios in the polypeptide chain. Interestingly, D,L-Lys-co-gly and D,L-Lys-co-Phe copolypeptides with the same composition ratio have comparable attenuating effects on fibrillation. The copolypeptide with highest molar fraction of glycine residue exhibits the strongest suppression of HEWL fibrillation. The copolypeptide has the highest hydrophobic interacting capacity due to the more molar ratio of apolar monomer in the polymer backbone. The major driving forces for the association of HEWL and copolypeptides are likely to be hydrogen bonding and hydrophobic interactions, and these interactions reduce the concentration of free protein in solution available to proceed to fibrillation, leading to the increase of lag time and attenuation of fibrillation. The results of this work may contribute to the understanding of the molecular factors affecting amyloid fibrillation and the molecular mechanism(s) of the interactions between the unstructured polypeptides and the amyloid proteins.

Interaction of polymers with amyloidogenic peptides

“…Hybrid copolymers, composed of both a synthetic polymer segment and amino acids, are of interest to drive, with a single macromolecule, several types of interaction. The fibrillation of hen‐egg‐white lysozyme (HEWL) in the absence or presence of d ‐ l ‐lysine‐ co ‐glycine ( d,l ‐Lys‐ co ‐Gly) and d ‐ l ‐lysine‐ co ‐ l ‐phenylalanine ( d,l ‐Lys‐ co ‐Phe) copolypeptides evidences that reduction or acceleration of fibrillation depends on the polypeptide concentration and composition ratios in the polypeptide chains . Comparable composition ratios induce similar attenuating effects on fibrillation.…”