Abstract
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).
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Piron, J., Tourwé, D. (2001). Stereoselective Synthesis of Transition State Analog Inhibitors of DPP-IV Using 2-Substituted Thiazoles. In: Lebl, M., Houghten, R.A. (eds) Peptides: The Wave of the Future. American Peptide Symposia, vol 7. Springer, Dordrecht. https://doi.org/10.1007/978-94-010-0464-0_67
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DOI: https://doi.org/10.1007/978-94-010-0464-0_67
Publisher Name: Springer, Dordrecht
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