(308c) Helix Stabilization of Poly(ethylene glycol)-Peptide Conjugates

Synthetic polymer-protein conjugates can improve biomolecule function over natural proteins. In the case of helix forming polypeptides, these hybrid biomacromolecules offer the potential stabilization of peptide helicies to enhance their receptor binding, improve protease resistance, and cell membrane permeability. To gain insights into protein stabilization via polymer conjugation, we have performed replica exchange molecular dynamics simulations of a specific helix forming peptide (1CW) experimentally known to be stabilized by oligo(ethylene glycol). Ethylene glycol is found to preferentially interact with positively charged lysine and thereby stabilize hydrogen-bonding with neighboring amino acids. Side chain interference of lysine with its neighbors is reduced by ethylene glycol, with a consequential increase in helicity. Simulation of polyalanine with lysine mutations shows similar results. We therefore conclude the interaction of lysine with ethylene oxide contributes to helix stability.