Fluorinated alcohols can induce peptides and proteins to take up helical conformations. Nuclear Overhauser effect (NOE) spectroscopy experiments and analysis of C(alpha)H proton chemical shifts show that the conformation of melittin in 35% hexafluoro-2-propanol/water is alpha-helical from residues Ile-2 to Val-8 and from Leu-13 to Gln-25. As has been found in other solvent systems, the two helical regions are not colinear; the interhelix angle (73 +/- 15 degrees ) in 35% 1,1,1,3,3,3-hexafluoro-2-propanol/water is smaller than the angle found in other fluoroalcohol-water mixtures or in the crystal. Intermolecular (1)H(19)F and (1)H(1)H nuclear Overhauser effects were used to explore interaction of solvent components with melittin dissolved in this solvent mixture. The NOEs observed indicate that fluoroalcohol and water molecules are both tightly bound to the peptide in the vicinity of the interhelix bend. For the remainder of the molecule, solute-solvent NOEs are consistent with preferential solvation of the peptide by the fluoroalcohol component of the solvent mixture.
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 1H{19F} 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 approximately 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.
c 1.7, dioxane), and 160 mg (75%) of (Z)-2-benzyl-3-(4-methoxybenzoyl)propenoic acid (IV) as the only detectable products. Compound (+)-I has NMR, IR, mass spectrum, and chromatographic behavior identical with that of (±)-I. Compound IV has different spectral and chromatographic behavior than (E)-2benzyl-3-(4-methoxybenzoyl)propenoic acid (VII).
NMR (CDC13):3.72 (br s, 2 ), 3.81 (s, 3 ), 6.
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