Single-Molecule-Level Evidence for the Osmophobic Effect

摘要

Organic osmolytes are low-molecular-weight osmotically active compounds, which are ubiquitous in living systems and are able to modulate protein stability. Among them, those that act as folding agonists, enhancing the stability of the native structure of proteins, such as trimethylamine N-oxide, betaine, sarcosine, proline, trehalose, sucrose, glycerol, sorbitol, and dimethylsulphoxide (DMSO), are collectively called protecting osmolytes or "chemical chaperones".One rather puzzling feature of these compounds is that they are able to affect the folding of very diverse proteins in similar ways, suggesting that they might act according to a general mechanism, in contrast to the more specific mechanisms employed by chaperone proteins. In fact, the most widely accepted theory to rationalize their mode of action proposes that the addition of a protecting osmolyte to water as a co-solvent results in diminished solvent quality for the protein backbone, thus making intra-peptide backbone-backbone hydrogen bonds energetically more favorable than those between the backbone and the solvent.