The preferred solid‐state conformation of (αMe)Trp peptides

The two Z‐l‐Ala‐dl‐(xMe)Trp‐NH2 diastereomeric dipeptides were synthesized from (Z‐l‐Ala)2O and H‐dl‐(xMe)Trp‐NH2. The latter racemate, prepared by phase‐transfer catalyzed alkylation of the Nα‐benzylidene derivative of alanine amide followed by acidic hydrolysis of the resulting Schiff base, was characterized by X‐ray diffraction. The molecular and crystal structure of Z‐l‐Ala‐l‐(αMe)Trp‐NH2, separated from its diastereomer by silica‐gel column chromatography, was determined by X‐ray diffraction analysis. Both independent molecules in the asymmetric unit of the dipeptide adopt a type‐II β‐bend conformation. However, only the more regularly folded conformation of molecule B is stabilized by a 1←4 C=O…H—N intramolecular H bond. The present results indicate that: (i) the Cα‐methylated (αMe)Trp residue is a strong β‐bend and helix former, and (ii) the relationship between (αMe)Trp chirality and helix screw sense tends to be opposite to that of protein amino acids. The implications for the use of the (αMe)Trp residue in designing conformationally restricted analogs of bioactive peptides are briefly discussed. ©Munksgaard 1995. Copyright © 1995, Wiley Blackwell. All rights reserve