Implications of excluded volume for chemical inhibition of protein fibrillation

摘要

Two quantitative models for the effect of high total macromolecular volume occupancy ('macromolecular crowding') upon the chemical inhibition of protein fibrillation are presented. The first assumes that fibrillation is reversible, and the second assumes that fibrillation is irreversible. Both models predict that small molecule inhibitors will be less effective in crowded media than in dilute media, whereas macromolecular inhibitors are likely to retain their efficiency in crowded media. It is suggested that the coupling of one or more small-molecule inhibitors to an "inert" macromolecular support will increase inhibition efficiency in crowded media.