Interactions of hexafluoro-2-propanol with the Trp-cage peptide

Fluoro alcohols present in aqueous solutions can alter the dominant conformations of peptides and proteins. The origins of these effects likely are related to the details of solute-fluoro alcohol interactions. Preferential interaction of the fluoro alcohol component of a fluoro alcohol-water mixture with peptide solutes has been demonstrated by several experimental approaches. In the present work, we have used H-1{F-19} intermolecular NOE experiments to examine interactions of hexafluoro-2-propanol in a 30% fluoro alcohol-50 mM phosphate buffer solvent mixture with the Trp-cage peptide (NLY IQW LKD GGP SSG RPP PS). The results show that the peptide is selectively solvated by hexafluoro-2-propanol to the extent that the fluoro alcohol concentration near the peptide may be 3 to 4 times higher than the nominal concentration of fluoro alcohol in the bulk sample. The observed NOEs indicate that peptide-fluoro alcohol interactions persist for times of the order of 1 ns at 5 degrees C. As the sample temperature is increased, the lifetimes of fluoro alcohol interactions with several exposed side chains decrease to the extent that the peptide hydrogen-solvent fluorine interactions appear to become diffusive in nature, with interaction lifetimes of similar to 0.03 ns. It is known that protein molecules can provide specific sites for binding small organic solvent molecules. Our work suggests that small peptides also have this ability and that the dynamics for such interactions can be site-specific.