Conformations of synthetic alamethicin fragments. Evidence for 310 helical folding from 270-MHz hydrogen-1 nuclear magnetic resonance and circular dichroism studies.

1H NMR studies at 270 MHz on the synthetic alamethicin fragments Z-Aib-Pro-Aib-Ala-Aib-Ala-OMe (1-6), Boc-Gln-Aib-Val-Aib-Gly-Leu-Aib-OMe (7-13), Boc-Leu-Aib-Pro-Val-Aib-OMe (12-16), and Boc-Gly-Leu-Aib-Pro-Val-Aib-OMe (11-16) have been carried out in CDCl3 and (CD3)2SO. The intramolecularly hydrogen bonded amide hydrogens in these peptides have been delineated by using solvent titration experiments and temperature coefficients of NH chemical shifts in (CD3)2SO. All the peptides adopt highly folded structures, characterized by intramolecular 4 leads to 1 hydrogen bonds. The 1-6 fragment adopts a 310 helical conformation with four hydrogen bonds, in agreement with earlier studies (Rao, Ch. P., Nagaraj, R., Rao, C. N. R., & Balaram, P. (1980) Biochemistry 19, 425-431]. The 7-13 fragment also appears to be folded in 310 helical fashion, although some intramolecular hydrogen bonds are loosened in (CD3)2-SO). The 11-16 fragment favors a structure with three intramolecular hydrogen bonds of the 4 leads to 1 and 5 leads to 1 types. CD studies in trifluoroethanol suggest a helical structure for the 1-13 and 1-17 fragments and alamethicin, while IR studies support a helical structure for the 1-13 peptide, stabilized by intramolecular hydrogen bonding. On the basis of fragment conformations and earlier studies of the stereochemistry of alpha-aminoisobutyric acid (Aib) containing peptides, a structure is suggested for the alamethicin backbone. A largely 310 helical folding pattern is postulated for the hydrophobic 1-17 segments, with a polar flexible C-terminal tripeptide.