title: Preferred conformation of peptides based on cycloaliphatic C(alpha,alpha)-disubstituted glycines: 1-amino-cycloundecane-1-carboxylic acid (Ac11c).
abstract: Two complete series of N-protected oligopeptide esters to the pentamer level from 1-amino-cycloundecane-1-carboxylic acid (Ac11c), an alpha-amino acid conformationally constrained through a medium-ring C(i)alpha<-->C(i)alpha cyclization, and either the L-Ala or Aib residue, along with the N-protected Ac11c monomer and homo-dimer alkylamides, have been synthesized by solution methods and fully characterized. The preferred conformation of these model peptides has been assessed in deuterochloroform solution by FT-IR absorption and 1H-NMR techniques. Furthermore, the molecular structures of one derivative (Z-Ac11c-OH) and two peptides (the tripeptide ester Z-Aib-Ac11c-Aib-OtBu and the pentapeptide ester Z-Ac11c-(Aib)2-Ac11c-Aib-OtBu) have been determined in the crystal state by X-ray diffraction. The experimental results support the view that beta-bends and 3(10)-helices are preferentially adopted by peptides rich in Ac11c, the second largest cycloaliphatic C(alpha,alpha)-disubstituted glycine known. This investigation has allowed the authors to approach the completion of a detailed conformational analysis of the whole 1-amino-cycloalkane-1-carboxylic acid (Ac(n)c, with n = 3-12) series, which represents the prerequisite for their recent proposal of the 'Ac(n)c scan' concept.
authors.affiliation: Biocrystallography Research Centre, CNR, Department of Chemistry, University of Naples Federico II, Napoli, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Saviano
authors.forename: R
authors.initials: R
authors.lastname: Iacovino
authors.forename: E
authors.initials: E
authors.lastname: Benedetti
authors.forename: V
authors.initials: V
authors.lastname: Moretto
authors.forename: A
authors.initials: A
authors.lastname: Banzato
authors.forename: F
authors.initials: F
authors.lastname: Formaggio
authors.forename: M
authors.initials: M
authors.lastname: Crisma
authors.forename: C
authors.initials: C
authors.lastname: Toniolo
mesh_terms: D000146:Acids, Carbocyclic / Q000737:chemistry*; D019281:Dimerization; D005998:Glycine / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D013055:Spectrophotometry, Infrared; D014961:X-Ray Diffraction
chemical_list: D000146:Acids, Carbocyclic; D010455:Peptides; D005998:Glycine