1H-Azepine-4-amino-4-carboxylic acid: a new α,α-disubstituted ornithine analogue capable of inducing helix conformations in short Ala-Aib pentapeptides.
A very efficient synthesis of orthogonally protected 1H-azepine-4-amino-4-carboxylic acid, abbreviated as Azn, a conformationally restricted analogue of ornithine, was realized. It was obtained on a gram scale in good overall yield in five steps, three of which did not require isolation of the intermediates, starting from the readily available 1-amino-4-oxo-cyclohexane-4-carboxylic acid. Both enantiomers were used for the preparation of pentapeptide models containing Ala, Aib, and Azn. Conformational studies using both spectroscopic techniques (NMR, CD) and molecular dynamics on model 5-mer peptides showed that the (R)-Azn isomer possesses a marked helicogenic effect.
DISMAB, Sezione di Chimica Organica A. Marchesini, Facoltà di Farmacia, Università degli Studi Milano, Via Venezian 21, 20133 Milano, Italy. sara.pellegrino@unimi.it
Sara
S
Pellegrino
Alessandro
A
Contini
Francesca
F
Clerici
Alessandro
A
Gori
Donatella
D
Nava
Maria Luisa
ML
Gelmi
D001381:Azepines / Q000737:chemistry*; D002264:Carboxylic Acids / Q000737:chemistry*; D008958:Models, Molecular; D009952:Ornithine / Q000031:analogs & derivatives* / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D013237:Stereoisomerism
C575669:1H-azepine-4-amino-4-carboxylic acid; D001381:Azepines; D002264:Carboxylic Acids; D010455:Peptides; D009952:Ornithine