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Natural Substrates of Dipeptidyl Peptidase IV

  • Ingrid De Meester
  • Christine Durinx
  • Gunther Bal
  • Paul Proost
  • Sofie Struyf
  • Filip Goossens
  • Koen Augustyns
  • Simon Scharpé
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 477)

Conclusions

During the last decade it has become clear that DPP IV may have various substrates in vivo and that the preferred peptide will depend on the localization and physiological circumstances. It is at present impossible to depict a certain chain length as the maximal acceptable substrate size as it turns out that the immediate surrounding and surface accessibility of the NH2-terminal dipeptide are determining the susceptibility for cleavage of a peptide.

From the above, it is clear that the result of dipeptide removal by DPP IV may vary from no effect over activation or change in receptor selectivity to inactivation of the substrate. Therefore, biological interpretation of assays that do not distinguish intact and modified peptides, should be interpreted with caution. Furthermore, collection and conservation of samples for peptide analysis should occur in the cold and if possible in the presence of appropriate protease inhibitors.

Clinical implications of peptide processing by DPP IV include that the therapeutic potential of peptides that are degraded by DPP IV may largely be enhanced by creating DPP IV-resistant, active analogues, and that the most suitable NH2-terminal modification may vary from one peptide to another.

Most exciting are the observations that the in vivo introduction of DPP IV specific inhibitors can enhance the levels of intact endogeneous peptides creating therapeutical perspectives (Hoist et al 1998). Extensive in vivo experiments to reveal whether DPP IV is a powerful and safe pharmaceutical target, are awaited with interest.

Keywords

Pancreatic Polypeptide Gastric Inhibitory Polypeptide Dipeptidyl Peptidase Islet Amyloid Polypeptide Growth Hormone Release Factor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Ingrid De Meester
    • 1
  • Christine Durinx
    • 1
  • Gunther Bal
    • 2
  • Paul Proost
    • 3
  • Sofie Struyf
    • 3
  • Filip Goossens
    • 1
  • Koen Augustyns
    • 2
  • Simon Scharpé
    • 1
  1. 1.Laboratory of Clinical BiochemistryUniversity of AntwerpWilrijkBelgium
  2. 2.Laboratory of Pharmaceutical ChemistryUniversity of AntwerpWilrijkBelgium
  3. 3.Laboratory of MolecularImmunology Rega Institute for Medical ResearchUniversity of LeuvenLeuvenBelgium

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