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

Abstract
Terminally blocked homotri- and homotetra-peptides from (alpha Me)Leu, a chiral C-alpha-methylated. gamma-branched alpha-amino acid, have been prepared by solution methods and fully characterized. The molecular and crystal structures of pBrBz-[D-(alpha Me) Leu](3)-OH monohydrate and pBrBz-[D-(alpha Me)-Leu](4)-OBu(t) (where pBrBz indicates p-bromobenzoyl) were determined by X-ray diffraction. The tripeptide carboxylic acid adopts a type-III beta-turn conformation followed by an uncommon oxyanalogue of a type-III beta-turn, the latter being stabilized by a 1<--4 C=O...H-O intramolecular H-bond. The three independent molecules in the asymmetric unit of the tetrapeptide ester are folded in a regular right-handed 3(10)-helix. All (alpha Me)Leu residues exhibit phi, psi torsion angles in the helical region of the conformational map. These results indicate that: (i) the (alpha Me)Leu residue is an effective beta-turn and helix promoter and (ii) the relationship between (alpha Me)Leu chirality and turn and helix handedness is the same as that shown by the gamma-branched (alpha Me)Phe residue. but it is opposite to that characteristic of isovaline (Iva). with a linear side chain. the beta-branched (alpha Me)Val residue and protein amino acids (including Leu)

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