Hemorphins: substrates and/or inhibitors of dipeptidyl peptidase Ⅳ Hemorphins N-terminus sequence influence on the interaction between hemorphins and DPPIV

摘要

Hemorphins are endogenous peptides belonging to the family of "atypical" opioid peptides released from sequentially hydrolyzed hemoglobin. In this paper, we report an inhibitory effect of these peptides on dipeptidyl peptidase Ⅳ (DPPIV) activity, known to be involved in regulatory functions such as the activation or inactivation of peptides. The structure activity research revealed that hemorphins N-terminus sequence influences nature of the interaction between hemorphins and DPPIV. Kinetic studies conducted with purified DPPIV demonstrated that hemorphin-7 (H7) constitutes a good substrate (K_(cat)/K_m of 137 mM~(-1) s~(-1)) for this enzyme but could also act as a selective competitive inhibitor by substrate binding site competition. These blood-derived peptides could represent endogenous regulators of this enzyme activity.