Abstract: | The molecular and crystal structures of one derivative and three model peptides (to the pentapeptide level) of the chiral Cα,α-disubstituted glycine Cα-methyl, Cα-isopropylglycine (αMe)Val] have been determined by X-ray diffraction. The derivative is mClAc-l -(α Me)Val-OH, and the peptides are Z-l -(αMe)Val-(l -Ala)2-OMe monohydrate, Z-Aib-L-(αMe)Val-(Aib)2-OtBu, and Ac-(Aib)2-l -(αMe)Val-(Aib)2OtBu acetonitrile solvate. The tripeptide adopts a type-I β-turn conformation stabilized by a 1 ← 4N-H . O=C intramolecular H-bond. The tetra- and pentapeptides are folded in regular right-handed 310-helices. All four L-(αMe)Val residues prefer φ, Ψ angles in the right-handed helical region of the conformational map. The results indicate that: (i) the (αMe)Val residue is a strong type-I/III β-turn and helix former, and (ii) the relationship between (αMe)Val chirality and helix screw sense is the same as that of Cα-monosubstituted protein amino-acids. The implications for the use of the (αMe)Val residue in designing conformationally constrained analogues of bioactive peptides are briefly discussed. |