Further evidence for 2-alkyl-2-carboxyazetidines as gamma-turn inducers.
Reverse turns, a common motif in proteins and peptides, have attracted attention due to their relevance in a wide variety of biological processes. In an attempt to artificially imitate and stabilize these turns in short peptides, we have developed versatile synthetic methodologies for the preparation of 2-alkyl-2-carboxyazetidines and incorporated them into the i + 1 position of model tetrapeptides, where they have shown a tendency to induce gamma-turns. However, to ascertain the general utility of these restricted amino acids as gamma-type reverse turn inducers, it was then required to study the conformational preferences when located at other positions. To this end, model tetrapeptides R-CO-Ala-Xaa-NHMe, containing differently substituted azetidine moieties (Xaa = Aze, 2-MeAze, 2-BnAze) at the i + 2 position, were synthesized and subjected to a thorough conformational analysis. The theoretical and experimental results obtained, including the X-ray diffraction structure of a dipeptide derivative containing this skeleton, provide evidence that the 2-alkyl-2-carboxyazetidine scaffold is able to efficiently induce gamma-turns when incorporated into these short peptides, irrespective of their localization in the peptide chain.
Baeza
José Luis
JL
Instituto de Química Médica (CSIC), Juan de la Cierva 3, 28006 Madrid, Spain.
Gerona-Navarro
Guillermo
G
Thompson
Kevin
K
Pérez de Vega
M Jesús
MJ
Infantes
Lourdes
L
García-López
M Teresa
MT
González-Muñiz
Rosario
R
Martín-Martínez
Mercedes
M
D001384:Azetidines / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D021241:Spectrometry, Mass, Electrospray Ionization; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
D001384:Azetidines