CONFORMATIONAL STUDY BASED ON SIMULATED ANNEALING AND H-1 NMR OF PEPTIDES COMPRISING THE CONSENSUS SEQUENCE ARG(5)-ASP-VAL-ARG-GLY(9) - EFFECTS OF THE SUBSTITUTION SER-12 BY ALA-12 OR OF 3 RESIDUES DELETION ATTHE N-TERMINUS

A conformational search by simulated annealing has been performed on t wo peptides derivated from the tetradecapeptide used to isolate the Xe nopus laevis skin maturation RXVRG-endoprotease. The Ala 12 derivative , obtained by substitution in the hydrophobic C terminal fragment and the undecapeptide 4-14, obtained by deletion of an acidic rich tripept ide, were studied. No unique structure has been found for the tetradec apeptide Ala 12. This structural disorganization could explain the los s of activity of the endoprotease towards the subsituted peptide. For the undecapeptide, two different models in accordance with the NMR dat a were found. The conformational differences between these two models are locat ed in the consensus sequence and in each case an hairpin-lik e conformation is observed. These results could be related to the enha nced cleavage activity of the maturation enzyme. The obtained structur es are also compared with those of the original tetradecapeptide.dagge r