Conformational Characterization of the 1-Aminocyclobutane-1-carboxylic Acid Residue in Model Peptides

✍ Scribed by Maddalena Gatos; Fernando Formaggio; Marco Crisma; Claudio Toniolo; Gian Maria Bonora; Zettore Benedetti; Benedetto Di Blasio; Rosa Iacovino; Antonello Santini; Michele Saviano; Johan Kamphuis

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 185 KB
• Volume: 3
• Category: Article
• ISSN: 1075-2617
• DOI: 10.1002/(sici)1099-1387(199703)3:2<110::aid-psc88>3.0.co;2-6

✦ Synopsis

A series of N-and C-protected, monodispersed homo-oligopeptides (to the dodecamer level) from the small-ring alicyclic C a,a -dialkylated glycine 1-aminocyclobutane-1-carboxylic acid (Ac 4 c) and two Ala/Ac 4 c tripeptides were synthesized by solution methods and fully characterized. The conformational preferences of all the model peptides were determined in deuterochloroform solution by FT-IR absorption and 1 H-NMR. The molecular structures of the amino acid derivatives Z-Ac 4 c-OH and Z 2 -Ac 4 c-OH, the tripeptides Z-(Ac 4 c) 3 -OtBu, Z-Ac 4 c-(L-Ala) 2 -OMe and Z-L-Ala-Ac 4 c-L-Ala-OMe, and the tetrapeptide Z-(Ac 4 c) 4 -OtBu were determined in the crystal state by X-ray diffraction. The average geometry of the cyclobutyl moiety of the Ac 4 c residue was assessed and the t(N-C a -C 0 ) bond angle was found to be significantly expanded from the regular tetrahedral value. The conformational data are strongly in favour of the conclusion that the Ac 4 c residue is an effective b-turn and helix former. A comparison with the structural propensities of a-aminoisobutyric acid, the prototype of C a,a -dialkylated glycines, and the other extensively investigated members of the family of 1aminocycloalkane-1-carboxylic acids (Ac n c, with n 3, 5-8) is made and the implications for the use of the Ac 4 c residue in conformationally constrained peptide analogues are briefly examined.