Fully and partially DPIV-resistant analogs of GIP
1–30 could be synthesized. The introduction of D-amino acids in P1- and P1’-position resulted in a slight reduction in binding
and bioactivity. The examined C-terminal truncated fragments (with exception of the GIP
1–30 fragment) showed no binding affinity, whereas the antagonistic N-terminal truncated fragments were able to bind to transfected
rat GIP receptor. These results emphasize the hypothesis of an existing one-receptor-two-interaction-sites-model which was
shown for peptides of the GRF-family.
Concerning the potential use of GIP analogs in the treatment of type II diabetes mellitus, these results offer the possibility
to synthesize analogs with reasonable half-life times and physiologically relevant binding affinities and bioactivity.
Key words dipeptidyl peptidase IV - glucose-dependent insulinotropic peptide