H-1-NMR CONFORMATIONAL STUDY ON N-TERMINAL NONAPEPTIDE SEQUENCES OF HIV-1 TAT PROTEIN - A CONTRIBUTION TO STRUCTURE-ACTIVITY-RELATIONSHIPS

On the basis of our recent results. the N-terminal sequence of HIV-1 T at protein as a natural competitive inhibitor of dipeptidyl peptidase IV (DP IV) is supposed to interact directly with the active site of DP IV hence mediating its immunosuppressive effects via specific DP IV i nteractions. Of special interest is the finding that amino acid substi tutions of the Tat(1-9) peptide (MDPVDPNIE) in position 5 with S-isole ucine and in position 6 with S-leucine led to peptides with strongly r educed inhibitory activity suggesting differences in the solution conf ormation of the three analogues. Therefore, H-1 NMR techniques in conj unction with molecular modelling have been used here to determine the solution structure of Tat(1-9), I-5-Tat(1-9) and L-6-Tat(1-9) and to e xamine the influence of amino acid exchanges on structural features of these peptides. The defined structures revealed differences in the co nformations what might be the reason for different interactions of the se Tat(1-9) analogues with certain amino acids of the active site of D P IV. (C) 1998 European Peptide Society and John Wiley & Sons, Ltd.