1H NMR conformational study on n-terminal nonapeptide sequences of HIV-1 Tat protein: a contribution to structure–activity relationships
Corresponding Author
Carmen Mrestani-Klaus
Department of Biochemistry and Biotechnology, Institute of Biochemistry, Martin-Luther-University Halle-Wittenberg, Halle, Germany
Department of Biochemistry and Biotechnology, Institute of Biochemistry, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Str. 3, D-06120 Halle, GermanySearch for more papers by this authorAnnett Fengler
Department of Biochemistry and Biotechnology, Institute of Biochemistry, Martin-Luther-University Halle-Wittenberg, Halle, Germany
Search for more papers by this authorWolfgang Brandt
Department of Biochemistry and Biotechnology, Institute of Biochemistry, Martin-Luther-University Halle-Wittenberg, Halle, Germany
Search for more papers by this authorJürgen Faust
Department of Biochemistry and Biotechnology, Institute of Biochemistry, Martin-Luther-University Halle-Wittenberg, Halle, Germany
Search for more papers by this authorSabine Wrenger
Center for Internal Medicine, Institute of Experimental Internal Medicine, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany
Search for more papers by this authorDirk Reinhold
Center for Internal Medicine, Institute of Experimental Internal Medicine, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany
Search for more papers by this authorSiegfried Ansorge
Center for Internal Medicine, Institute of Experimental Internal Medicine, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany
Search for more papers by this authorKlaus Neubert
Department of Biochemistry and Biotechnology, Institute of Biochemistry, Martin-Luther-University Halle-Wittenberg, Halle, Germany
Search for more papers by this authorCorresponding Author
Carmen Mrestani-Klaus
Department of Biochemistry and Biotechnology, Institute of Biochemistry, Martin-Luther-University Halle-Wittenberg, Halle, Germany
Department of Biochemistry and Biotechnology, Institute of Biochemistry, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Str. 3, D-06120 Halle, GermanySearch for more papers by this authorAnnett Fengler
Department of Biochemistry and Biotechnology, Institute of Biochemistry, Martin-Luther-University Halle-Wittenberg, Halle, Germany
Search for more papers by this authorWolfgang Brandt
Department of Biochemistry and Biotechnology, Institute of Biochemistry, Martin-Luther-University Halle-Wittenberg, Halle, Germany
Search for more papers by this authorJürgen Faust
Department of Biochemistry and Biotechnology, Institute of Biochemistry, Martin-Luther-University Halle-Wittenberg, Halle, Germany
Search for more papers by this authorSabine Wrenger
Center for Internal Medicine, Institute of Experimental Internal Medicine, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany
Search for more papers by this authorDirk Reinhold
Center for Internal Medicine, Institute of Experimental Internal Medicine, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany
Search for more papers by this authorSiegfried Ansorge
Center for Internal Medicine, Institute of Experimental Internal Medicine, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany
Search for more papers by this authorKlaus Neubert
Department of Biochemistry and Biotechnology, Institute of Biochemistry, Martin-Luther-University Halle-Wittenberg, Halle, Germany
Search for more papers by this authorAbstract
On the basis of our recent results, the N-terminal sequence of HIV-1 Tat 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 interactions. Of special interest is the finding that amino acid substitutions of the Tat(1–9) peptide (MDPVDPNIE) in position 5 with S-isoleucine and in position 6 with S-leucine led to peptides with strongly reduced inhibitory activity suggesting differences in the solution conformation of the three analogues. Therefore, 1H NMR techniques in conjunction with molecular modelling have been used here to determine the solution structure of Tat(1–9), I5-Tat(1–9) and L6-Tat(1–9) and to examine the influence of amino acid exchanges on structural features of these peptides. The defined structures revealed differences in the conformations what might be the reason for different interactions of these Tat(1–9) analogues with certain amino acids of the active site of DP IV. © 1998 European Peptide Society and John Wiley & Sons, Ltd.
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