Stereoselective Synthesis of Transition State Analog Inhibitors of DPP-IV Using 2-Substituted Thiazoles

  • J. Piron
  • D. Tourwé
Part of the American Peptide Symposia book series (APSY, volume 7)


Dipeptidylpeptidase IV or DPP-IV belongs to the class of serine proteases and catalyzes the cleavage of dipeptides at the amino terminus of peptides. Natural substrates of DPP-IV are peptides such as substance P, β-casomorphin, monomeric fibrin, pro-melittin and hGHRH. Two high affinity inhibitors for DPP-IV are the tripeptides Diprotin A (Ile-Pro-Ile) and Diprotin B (Val-Pro-Leu) [1]. The most effective is Diprotin A with an IC50 value in the μM range, but it suffers from rapid enzymatic degradation. In order to prepare more stable analogues and to test the influence on the inhibitory properties, we used a convergent synthetic method to prepare several Pro-lie isosteres (Figure 1).


Crystallization Hydroxyl Hexane Amide Aldehyde 


  1. 1.
    Rahfeld, J., et al. Biochim. Biophys. Acta 1076, 314–316 (1991).PubMedCrossRefGoogle Scholar
  2. 2.
    Fehrentz, J.-A., Castro, B. Synthesis 676–678 (1983).Google Scholar
  3. 3.
    Dondoni, A. In Scheffold, R. (Ed.) Modem Synthetic Methods, Verlag Helvetica Chimica Acta, Basel, 1992, pp. 377–437.Google Scholar
  4. 4.
    Tourwé, D., et al. Tetrahedron Lett. 34, 5499–5502 (1993).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2001

Authors and Affiliations

  • J. Piron
    • 1
  • D. Tourwé
    • 1
  1. 1.Department of Organic ChemistryVrije Universiteit BrusselBrusselsBelgium

Personalised recommendations