DISTRIBUTION OF HELICITY WITHIN THE MODEL PEPTIDE ACETYL(AAQAA)(3)AMIDE

A series of peptides having the sequence acetyl(AAQAA(3))amide was synthesized each containing a different residue having its carbonyl carbon enriched in C-13. Th, resonance of each enriched carbonyl carbon was examined in aqueous solvents containing different concentrations of D2O, methanol, salt, and acid at a variety of temperatures. The thermal dependence of the carbonyl carbon chemical shift of each residue was analyzed in terms of a two-state helix/coil transition. The line shape observed for the carbonyl carbon of each residue in a D2O/H2O mixture was analyzed in terms of the backbone hydrogen bonding content of the amide group of the adjacent residue at equilibrium. The collective results indicate that the N-terminal region of the peptide is more helical than predicted by the traditional Lifson-Roig statistical mechanical model. The observed residue distribution of helical content can be simulated at 0 degrees C in water using a modified form of the Lifson-Roig model, an acetyl interaction of -1.22 kcal/mol, and propagation, s, values for the alanine and glutamine residues of 1.47 and 0.50, respectively. These values are very comparable with those obtained (Chakrabartty, A.; Kortemme, T.; Baldwin, R. L. Protein Sci. 1994, 3, 843-852) by analysis of isothermal mean residue ellipticity measurements of a series of host/guest peptides using an alternative modified Lifson-Roig model.