Effect of positive charge in VIP (16)gamma-glutamyl diamino derivatives on hVPAC1 and hVPAC2 receptor function

摘要

Increase of VPAC receptor s binding to the (16)gamma-glutamyl diaminopropane vasoactive intestinal peptide (VIP-DAP) agonist, a vasoactive intestinal polypeptide (VIP) structural analogue containing a positive charge at position 16, has confirmed the importance of a positive charge at this site. By investigating the effect of distance from the peptide backbone C alpha of a positive charge in position 16, data are reported here concerning: (I) a novel chemical method used for the synthesis of a new family of (16)gamma-glutamyl diamine VIP derivatives differing among them for single carbon atoms and including diammoethane (VIP-DAE2), diaminopropane (VIP-DAP3), diaminobutane (VIP-DAB4), diaminopentane (VIP-DAP5), and diaminohexane (VIP-DAH6); (ii) functional characterization of these compounds on human VPAC1 and VPAC2 receptors. In more detail, the EC50 and IC50 values, when measured as a function of the alkylic chain length, show in more detail, that the use of VIP-DAB4 derivative changes the IC50 but not the EC50, thus indicating on hVPAC2 receptor an unexpected relationship between binding and activity that differs from that obtained on hVPAC 1. Copyright (C) 2007 European Peptide Society and John Wiley & Sons, Ltd.