OBSERVATION OF WATER-MEDIATED HELIX-TERMINATING CONFORMATION IN A DEHYDROPHENYLALANINE PEPTIDE - CRYSTAL AND SOLUTION STRUCTURE OF THE OCTAPEPTIDE TA-PHE-VAL-DELTA-PHE-PHE-ALA-VAL-DELTA-PHE-GLY-OME

We have synthesised and determined the solution conformation and X-ray crystal structure of the octapeptide Ac-Delta Phe(1)-Val(2)-Delta Phe (3)-Phe(4)-Ala(5)-Val(6)-Delta Phe(7)-Gly(8)-OCH3 (Delta Phe = alpha,b eta-dehydrophenylalanine) containing three Delta Phe residues as confo rmation constraining residues. In the solid state, the peptide folds i nto (i) an N-terminal (3)10(R)-helical pentapeptide segment, (ii) a mi ddle non-helical segment, and (iii) a C-terminal incipient (3)10(L)-he lical segment. The results of H-1 NMR data also suggest that a similar multiple-turn conformation for the peptide is largely maintained in s olution. Though the C-terminal helix is incipient, the overall conform ation of the octapeptide matches well with the conformation of the hai rpins reported. Comparison of the pi-turn seen in the octapeptide mole cule with those observed in proteins at the C-terminal end of helixes shows the structural similarity among them. A water molecule mediates the 5 --> 2 hydrogen bond in the pi-turn region. This is the first exa mple of a water-inserted pi-turn in oligopeptides reported so far. Com parison between the present octapeptide and another (3)10(R)-helical d ehydro nonapeptide Boc-Val-Delta Phe-Phe-Ala-Phe-Delta Phe-Val-Delta P he-Gly-OCH3 solved by us recently, demonstrates the possible sequence- dependent conformational variations in alpha,beta-dehydrophenylalanine -containing oligopeptides.