title: Is the backbone conformation of C(alpha)-methyl proline restricted to a single region?
abstract: C(alpha)-methyl-L-proline, or L-(alphaMe)Pro, is probably the most conformationally constrained alpha-amino acid. In particular, its omega and phi torsion angles are restricted to about 180 and -60 degrees, respectively, and only three ranges of values are theoretically available for psi in mono- or longer peptides, namely, about -30 degrees (cis', 3(10)/alpha-helical structure), 60 degrees (inverse gamma turn), or 140 degrees (trans', poly(L-Pro)(n) II structure). In this work, we examined the tendency of a number of N(alpha)-acyl dipeptide N'-alkylamides of the type RCO-(alphaMe)Pro-Xxx-NHR' or RCO-Xxx-(alphaMe)Pro-NHR', in which Xxx is L (or D)-Ala, Aib (alpha-aminoisoburyric acid), or L (or D)-(alphaMe)Pro, long enough to fold into intramolecularly hydrogen-bonded gamma or beta turns. The results are compared with those obtained for the corresponding dipeptides based on Pro, a well-known turn-forming residue. For the crystal-state 3D-structural analysis we used X-ray diffraction, whereas our solution conformational analysis was heavily based on the FTIR absorption and (1)H and (13)C NMR spectroscopy techniques. We conclude that (alphaMe)Pro is able to explore both trans' and cis' psi areas of the conformational space, but in (alphaMe)Pro the latter is overwhelmingly more populated, in marked contrast to the Pro preference. This finding is a clear indication that in (alphaMe)Pro the major 3D-structural determinant is the C(alpha)-methyl group. The circular dichroism (CD) signature of a peptide type III' beta-turn conformation is also proposed.
authors: Institute of Biomolecular Chemistry, CNR, Padova Unit, Department of Chemistry, University of Padova via Marzolo 1, 35131 Padova (Italy), Fax: (+39) 049-827-5239.
authors: Matteo
authors: M
authors: De Poli
authors: Institute of Biomolecular Chemistry, CNR, Padova Unit, Department of Chemistry, University of Padova via Marzolo 1, 35131 Padova (Italy), Fax: (+39) 049-827-5239.
authors: Alessandro
authors: A
authors: Moretto
authors: Institute of Biomolecular Chemistry, CNR, Padova Unit, Department of Chemistry, University of Padova via Marzolo 1, 35131 Padova (Italy), Fax: (+39) 049-827-5239.
authors: Marco
authors: M
authors: Crisma
authors: Institute of Biomolecular Chemistry, CNR, Padova Unit, Department of Chemistry, University of Padova via Marzolo 1, 35131 Padova (Italy), Fax: (+39) 049-827-5239.
authors: Cristina
authors: C
authors: Peggion
authors: Institute of Biomolecular Chemistry, CNR, Padova Unit, Department of Chemistry, University of Padova via Marzolo 1, 35131 Padova (Italy), Fax: (+39) 049-827-5239.
authors: Fernando
authors: F
authors: Formaggio
authors: DSM Pharmaceutical Products, Innovative Synthesis and Catalysis, P.O. Box 18, 6160 MD Geleen (The Netherlands).
authors: Bernard
authors: B
authors: Kaptein
authors: DSM Pharmaceutical Products, Innovative Synthesis and Catalysis, P.O. Box 18, 6160 MD Geleen (The Netherlands).
authors: Quirinus B
authors: QB
authors: Broxterman
authors: Institute of Biomolecular Chemistry, CNR, Padova Unit, Department of Chemistry, University of Padova via Marzolo 1, 35131 Padova (Italy), Fax: (+39) 049-827-5239.
authors: Claudio
authors: C
authors: Toniolo
mesh_terms: D018360:Crystallography, X-Ray; D004151:Dipeptides / Q000737:chemistry*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D011392:Proline / Q000031:analogs & derivatives* / Q000737:chemistry; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D013237:Stereoisomerism
chemical_list: D004151:Dipeptides; C051624:2-methylproline; D011392:Proline