C(alpha)-methyl proline: a unique example of split personality.
Methylation at the C(alpha)-position of a Pro residue was expected to lock the preceding tertiary amide (omega) torsion angle of the resulting (alphaMe)Pro to the trans disposition and to restrict the phi,psi surface to the single region where the 3(10)/alpha-helices are found (in this five-membered ring residue phi is severely constrained to about +/-65 degrees by its cyclic nature). The results of the present X-ray diffraction work on a selected set of four N(alpha)-blocked, (alphaMe)Pro-containing, dipeptide N'-alkylamides clearly show that, although the region of the conformational map largely preferred by (alphaMe)Pro would indeed be that typical of 3(10)/alpha-helices, the semi-extended [type-II poly(Pro)(n) helix] region can also be explored by this extremely sterically demanding C(alpha)-tetrasubstituted alpha-amino acid. In addition, the known high propensity for beta-turn formation of the Pro residue is further enhanced in peptides based on its C(alpha)-methylated derivative.
Moretto
Alessandro
A
Department of Chemistry, University of Padova, Institute of Biomolecular Chemistry, 35131 Padova, Italy.
Terrenzani
Francesco
F
Crisma
Marco
M
Formaggio
Fernando
F
Kaptein
Bernard
B
Broxterman
Quirinus B
QB
Toniolo
Claudio
C
D018360:Crystallography, X-Ray; D004151:Dipeptides / Q000737:chemistry*; D007536:Isomerism; D008745:Methylation; D008958:Models, Molecular; D011392:Proline / Q000031:analogs & derivatives* / Q000737:chemistry*; D011487:Protein Conformation