Amphiphilic structured PEG derivatives suppressing protein thermal aggregation at extremely low molecular ratio

Abstract

Amphiphilic structured PEG derivatives consisting of octa(ethylene glycol) chains connected with aromatic vertices inhibited the thermally-induced lysozyme aggregation even when present at below 0.1 mM concentration. This concentration range is close to a 1:1 molar ratio with the additive and lysozyme, and was completely inaccessible for previously reported stabilizers. The possible mechanisms of the stabilizing actions revealed that the PEG-based amphiphiles do not in fact prevent aggregation at the molecular level, as assumed before, but rather prevent macroscopic precipitation of the denatured protein molecules and enable dissolution of them to the native, folded state at ambient temperature. The stabilizers do not interact with properly folded native lysozyme and therefore do not affect its natural catalytic properties, indicating a potential for practical use in protein-based therapeutics.