title: Azetidine-derived amino acids versus proline derivatives. alternative trends in reverse turn induction.
abstract: The influence of 2-alkyl-2-carboxyazetidines (Aze) on the 3D structure of model tetrapeptides R2CO-2-R1Aze-l-Ala-NHMe has been analyzed by molecular modeling, 1H NMR, and FT-IR studies. The conformational constraints introduced by the four-membered ring resulted in an effective way to stabilize gamma-turn-like conformations in these short peptides. The conformational preferences of these Aze-containing peptides have been compared to those of the corresponding peptide analogues containing Pro or alpha-MePro in the place of 2-alkyl-Aze residue. In the model studied, both Pro and Aze derivatives are able to induce reverse turns, but the nature of the turn is different as a function of the ring size. While the five-membered ring of Pro tends to induce beta-turns, as previously suggested by different authors, the four-membered ring of Aze residues forces the peptide to preferentially adopt gamma-turn conformations. In both cases, the presence of an alkyl group at the alpha-position of Pro or the azetidine-2-carboxylate ring enhances significantly the turn-inducing ability. These results might open the opportunity of using 2-alkyl-Aze residues as versatile tools in defining the role of gamma-turn structures within the bioactive conformation of selected peptides, and represent an alternative to Pro derivatives as turn inducers.
authors.affiliation: Instituto de Química Médica (CSIC), Juan de la Cierva 3, 28006 Madrid, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Baeza
authors.forename: Guillermo
authors.initials: G
authors.lastname: Gerona-Navarro
authors.forename: M Jesús
authors.initials: MJ
authors.lastname: Pérez de Vega
authors.forename: M Teresa
authors.initials: MT
authors.lastname: García-López
authors.forename: Rosario
authors.initials: R
authors.lastname: Gonzalez-Muñiz
authors.forename: Mercedes
authors.initials: M
authors.lastname: Martín-Martínez
mesh_terms: D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D001384:Azetidines / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D011392:Proline / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D001384:Azetidines; C082735:azetidine; D011392:Proline