ALPHA,BETA-DEHYDRO-AMINO ACID RESIDUES IN THE DESIGN OF PEPTIDE STRUCTURES - SYNTHESIS, CRYSTAL-STRUCTURE, AND MOLECULAR-CONFORMATION OF 2 HOMOLOGOUS PEPTIDES - N-AC-DEHYDRO-PHE-L-LEU-OCH3 AND N-AC-DEHYDRO-PHE-NORVAL-OCH3

The dehydro-residue containing peptides N-Ac-dehydro-Phe-L-Leu-OCH3 (I) and N-Ac-dehydro-Phe-NorVal-OCH3 (II) were synthesized by the usual workup procedures. The peptides crystallize from their solutions in methanol in space group P6(5): (I) a = b = 12.528(2) Angstrom, c = 21.653(5) Angstrom; (II) a = b = 12.532(2) Angstrom, c = 21.695(4) Angstrom. The structures were determined by direct methods. Both peptides adopt similar conformations with phi,psi of dehydro-Phe as follows: (I) -57.0(5)degrees and -37.0(5)degrees; (II) -56.0(5),degrees and -37.5(5)degrees. The observed data on dehydro-Phe when placed at the (i + 1) position show that the phi,psi values of dehydro-Phe are either -60 degrees, 140 degrees or -60 degrees, -30 degrees. The conformation of -60 degrees, 140 degrees can be accommodated only with a flexible residue at the (i + 2) position while the phi,psi values of -60 degrees, -30 degrees are obtained with a bulky residue at the (i + 2) position as in the present structures. The molecules are packed in a helical way along the c axis. These are held by two strong intermolecular hydrogen bonds involving both NH as donors and acetyl group and dehydro-Phe oxygen atoms as accepters. (C) 1994 John Wiley & Sons, Inc.