Cα-Methyl proline: A unique example of split personality

Abstract

Methylation at the C^α-position of a Pro residue was expected to lock the preceding tertiary amide (ω) torsion angle of the resulting (αMe)Pro to the trans disposition and to restrict the ϕ,ψ surface to the single region where the 3₁₀/α-helices are found (in this five-membered ring residue ϕ is severely constrained to about ±65° by its cyclic nature). The results of the present X-ray diffraction work on a selected set of four N^α-blocked, (αMe)Pro-containing, dipeptide N′-alkylamides clearly show that, although the region of the conformational map largely preferred by (αMe)Pro would indeed be that typical of 3₁₀/α-helices, the semi-extended [type-II poly(Pro)_n helix] region can also be explored by this extremely sterically demanding C^α-tetrasubstituted α-amino acid. In addition, the known high propensity for β-turn formation of the Pro residue is further enhanced in peptides based on its C^α-methylated derivative. © 2007 Wiley Periodicals, Inc. Biopolymers 89: 465–470, 2008.

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