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Conformational Characterization of the 1‐Aminocyclobutane‐1‐carboxylic Acid Residue in Model Peptides
Author(s) -
Gatos Maddalena,
Formaggio Fernando,
Crisma Marco,
Toniolo Claudio,
Bonora Gian Maria,
Benedetti Zettore,
Di Blasio Benedetto,
Iacovino Rosa,
Santini Antonello,
Saviano Michele,
Kamphuis Johan
Publication year - 1997
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/(sici)1099-1387(199703)3:2<110::aid-psc88>3.0.co;2-6
Subject(s) - chemistry , tripeptide , residue (chemistry) , moiety , stereochemistry , tetrapeptide , peptide , amino acid , oligopeptide , organic chemistry , biochemistry
A series of N‐ and C‐protected, monodispersed homo‐oligopeptides (to the dodecamer level) from the small‐ring alicyclic C α,α ‐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 ‐O t Bu, 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 ‐O t Bu 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 τ(N–C α –C′) 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 β‐turn and helix former. A comparison with the structural propensities of α‐aminoisobutyric acid, the prototype of C α,α ‐dialkylated glycines, and the other extensively investigated members of the family of 1‐aminocycloalkane‐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. © 1997 European Peptide Society and John Wiley & Sons, Ltd