Turn stabilization in short peptides by C α ‐methylated α‐amino acids

The crystal‐state conformations of three protected tripeptides, four tetrapeptides, and one pentapeptide, heavily based on the chiral C α ‐methylated α‐amino acids Iva, (αMe)Nva, and (Me)Val, were assessed by X‐ray diffraction analyses. The eight peptide sequences are as follows: Z( D Iva) 2 D ValOMe, Z D Iva L IvaGlyO t Bu, Z L Pro D Iva L IvaGlyO t Bu, Z L Pro L Iva D IvaGlyO t Bu, ZAib[ L (αMe)Nva] 2 O t Bu, Ac[ L (αMe)Val] 3 D(αMe)ValO t Bu, Z[L(αMe)Val] 4 OH, and Z L Ala[ L (αMe)Nva] 4 O t Bu. Two independent molecules were observed in the asymmetric units of Z D Iva L IvaGlyO t Bu and ZAib[ L (αMe)Nva] 2 O t Bu, while three independent molecules were seen in Z L Ala[ L (αMe)Nva] 4 O t Bu. All peptides are folded in a single or multiple β‐turn conformations. Interestingly: (i) a water bridge within the N‐terminal β‐turn is seen in Z L Pro L Iva D IvaGlyO t Bu (dihydrate), and (ii) the hydroxyl group of the C‐terminal carboxyl functionality of Z[ L (αMe)Val] 4 OH generates an oxy‐analogue of a β‐turn. The N‐terminal β‐turn is missing in molecules A and B, but it does occur, although poorly stabilized, in molecule C, of Z L Ala[ L (αMe)Nva] 4 O t Bu. © 2004 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2005