Search

Research has been conducted on the 5.6-spirolactams. The conformational preference of these compounds has been investigated via the prepared Ac-{Gly-Leu}-Met-NH (sub)2 derivatives (S,S,S) and (S,R,S) with the tripeptidic C-terminal region present in tachykinins.

The productive synthesis of tetrapeptide containing cyclobutane and beta-alanine sediments is explained. Analytical computations predict a most stable folded conformation corresponding to a 14-helix stabilized by a hydrogen bond.

The efficient synthesis of tetrapeptide 5 containing, in alternation, cyclobutane and β-alanine residues is described. NMR experiments both at low temperature in CDCl3 and at 298 K in DMSOd6 solutions show the contribution of a strong hydrogen bond in the folded major conformation of 5. Temperature coefficients and diffusion times point out a hydrogen bond involving the NH proton from the cyclobutane residue 1 whereas NOEs manifest the high rigidity of the central fragment of the molecule and are compatible with a 14-membered macrocycle. Theoretical calculations predict 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 remains unaltered during the molecular dynamics simulation at 298 K in chloroform. All these results provide evidence for a 14-helical folding and reveal the ability of cis-2-aminocyclobutane carboxylic acid residues to promote folded conformations when incorporated into β-peptides. [ABSTRACT FROM AUTHOR]