Conformational studies in solid state and solution of protected C-terminaldipeptide fragment (Boc-Phe-Pro-NH2) of morphiceptin

The crystal structure of the protected C-terminal dipeptide fragment (Boc-P he-Pro-NH2) of the mu-opioid receptor highly selective agonist, morphicepti n (Tyr-Pro-Phe-Pro-NH2), was determined; the crystals are monoclinic with s pace group P2(1) and unit cell dimensions: a = 11.5731(5), b = 6.4490(3), c = 15.4082(5) Angstrom, beta = 100.359(5)degrees and Z = 2. To examine the influence of proline on the conformation of peptide bond, the molecular con formation was studied in solid state and solution (using H-1 and C-13 NMR d ata). The X-ray analysis revealed the following conformations of peptide ba ckbone: phi(1) = -63.2(5)degrees, psi(1) = 156.1(4)degrees, omega(1) = -174 .3(4)degrees, phi(2) = -66.0(5)degrees and psi(2) = 152.0(4)degrees. The co nformation of the Boc group is trans-trans. Experimental data revealed the trans conformation about the Phe-Pro amide bond, both in solid state and so lution (DMSO). The possibility of cis/trans isomerization about the peptide bond (omega(1)) was examined by theoretical calculations using BIOSYM soft ware. Molecular modelling, including molecular dynamics simulations of the title dipeptide, is in favour of trans peptide bond.