Position of side-chain branching and handedness of turns and helices of homopeptides from chiral C α -methylated amino acids. Crystal-state structural analysis of (αMe)Leu trimer and tetramer

Terminally blocked homotri- and homotetra-peptides from (αMe)Leu, a chiral Cα-methylated, γ-branched α-amino acid, have been prepared by solution methods and fully characterized. The molecular and crystal structures of pBrBz-[D-(αMe)Leu]3-OH monohydrate and pBrBz-[D-(αMe)-Leu]4-OBut(where pBrBz indicates p-bromobenzoyl) were determined by X-ray diffraction. The tripeptide carboxylic acid adopts a type-III β-turn conformation followed by an uncommon oxyanalogue of a type-III β-turn, the latter being stabilized by a 1â†�4 CO ⋯ H–O intramolecular H-bond. The three independent molecules in the asymmetric unit of the tetrapeptide ester are folded in a regular right-handed 310-helix. All (αMe)Leu residues exhibit φ, Ψ torsion angles in the helical region of the conformational map. These results indicate that: (i) the (αMe)Leu residue is an effective β-turn and helix promoter and (ii) the relationship between (αMe)Leu chirality and turn and helix handedness is the same as that shown by the γ-branched (αMe)Phe residue, but it is opposite to that characteristic of isovaline (Iva), with a linear side chain, the β-branched (αMe)Val residue and protein amino acids (including Leu).