CHARACTERIZATION AND VALIDATION OF INHIBITORS AND LIGANDS OF DIPEPTIDYL AMINOPEPTIDASE IV (DP IV)

摘要

The invention relates to a method for characterization and validation of inhibitors or ligands of DPIV, DP8 or DP9 by their interaction with specific binding sites in silico and in vitro. It describes the use of special binding properties at the binding site of the DPIV in the central pore of DPIV, which is distant from the catalytic domain by at least 10 Angström (1 nm) which is essential for the steric inhibition of this peptidase and related enzymes like DP8 and DP9 by DPIV ligands or steric inhibitors for the use of these compounds to suppress DNA synthesis of lymphocytes, dermal cells and other cells. This finding is also important in that this technique can be used to predict unwanted side effects of DPIV related drugs and exclude effects of DPIV inhibitors developed for the treatment of Diabetes mellitus type II on immune functions and vice versa.