Azetidine-derived amino acids versus proline derivatives. alternative trends in reverse turn induction.
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.
Baeza
José Luis
JL
Instituto de Química Médica (CSIC), Juan de la Cierva 3, 28006 Madrid, Spain.
Gerona-Navarro
Guillermo
G
Pérez de Vega
M Jesús
MJ
García-López
M Teresa
MT
Gonzalez-Muñiz
Rosario
R
Martín-Martínez
Mercedes
M
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*
D000596:Amino Acids; D001384:Azetidines; C082735:azetidine; D011392:Proline