14-Helical Folding in a Cyclobutane-ContainingTetrapeptide

IZQUIERDO, SANDRA; KOGAN, MARCELO J.; PARELLA, TEODOR; MOGLIONI, ALBERTINA G.; BRANCHADELL, VICENC; GIRALT, ERNEST; ORTUNO, ROSA M.

JOURNAL OF ORGANIC CHEMISTRY

AMER CHEMICAL SOC

Lugar: Washington; Año: 2004 vol. 69 p. 5093 - 5099

0022-3263

Tetrapeptide I, contg. aminocyclobutanecarboxylate and β-​alanine residues in alternation, was efficiently synthesized. NMR expts. at low temp. in CDCl3 and at 298 K in DMSO-​d6 solns. showed the presence of a strong hydrogen bond in the folded major conformation of I. Temp. coeffs. and diffusion times reflected a hydrogen bond involving the NH proton from the cyclobutane residue 1, whereas NOEs indicated the high rigidity of the central fragment of the mol. and were compatible with a 14-​membered macrocycle. Theor. calcns. predicted a most stable folded conformation corresponding to a 14-​helix stabilized by a hydrogen bond between NH10 in the first residue and OC25 in the third residue. This structure remained unaltered during the mol. dynamics simulation at 298 K in chloroform. These results provided evidence for a 14-​helical folding and showed that cis-​2-​aminocyclobutanecarboxylic acid can promote folded conformations when incorporated into β-​peptides