Is the backbone conformation of C(alpha)-methyl proline restricted to a single region?
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.
De Poli
Matteo
M
Institute of Biomolecular Chemistry, CNR, Padova Unit, Department of Chemistry, University of Padova via Marzolo 1, 35131 Padova (Italy), Fax: (+39) 049-827-5239.
Moretto
Alessandro
A
Institute of Biomolecular Chemistry, CNR, Padova Unit, Department of Chemistry, University of Padova via Marzolo 1, 35131 Padova (Italy), Fax: (+39) 049-827-5239.
Crisma
Marco
M
Institute of Biomolecular Chemistry, CNR, Padova Unit, Department of Chemistry, University of Padova via Marzolo 1, 35131 Padova (Italy), Fax: (+39) 049-827-5239.
Peggion
Cristina
C
Institute of Biomolecular Chemistry, CNR, Padova Unit, Department of Chemistry, University of Padova via Marzolo 1, 35131 Padova (Italy), Fax: (+39) 049-827-5239.
Formaggio
Fernando
F
Institute of Biomolecular Chemistry, CNR, Padova Unit, Department of Chemistry, University of Padova via Marzolo 1, 35131 Padova (Italy), Fax: (+39) 049-827-5239.
Kaptein
Bernard
B
DSM Pharmaceutical Products, Innovative Synthesis and Catalysis, P.O. Box 18, 6160 MD Geleen (The Netherlands).
Broxterman
Quirinus B
QB
DSM Pharmaceutical Products, Innovative Synthesis and Catalysis, P.O. Box 18, 6160 MD Geleen (The Netherlands).
Toniolo
Claudio
C
Institute of Biomolecular Chemistry, CNR, Padova Unit, Department of Chemistry, University of Padova via Marzolo 1, 35131 Padova (Italy), Fax: (+39) 049-827-5239.
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
D004151:Dipeptides; C051624:2-methylproline; D011392:Proline