Synthesis of dehydrodipeptide esters and their evaluation as inhibitors of cathepsin C

Maciej Makowski; Paweł Lenartowicz; Bartosz Oszywa; Michał Jewgiński; Małgorzata Pawełczak; Paweł Kafarski

doi:10.1007/s00044-015-1366-0

Synthesis of dehydrodipeptide esters and their evaluation as inhibitors of cathepsin C

Med Chem Res. 2015;24(8):3157-3165. doi: 10.1007/s00044-015-1366-0. Epub 2015 Apr 16.

Authors

Maciej Makowski¹, Paweł Lenartowicz¹, Bartosz Oszywa¹, Michał Jewgiński², Małgorzata Pawełczak¹, Paweł Kafarski³

Affiliations

¹ Faculty of Chemistry, Opole University, Oleska 48, 45-052 Opole, Poland.
² Department of Bioorganic Chemistry, Faculty of Chemistry, Wroclaw University of Technology, Wybrzeze Wyspianskiego 27, 50-370 Wroclaw, Poland.
³ Faculty of Chemistry, Opole University, Oleska 48, 45-052 Opole, Poland ; Department of Bioorganic Chemistry, Faculty of Chemistry, Wroclaw University of Technology, Wybrzeze Wyspianskiego 27, 50-370 Wroclaw, Poland.

Abstract

The procedures for the synthesis of esters of dehydropeptides containing C-terminal (Z)-dehydrophenylalanine and dehydroalanine have been elaborated. These esters appeared to be moderate or weak inhibitors of cathepsin C, with some of them exhibiting slow-binding behavior. As shown by molecular modeling, they are rather bound at the surface of the enzyme and are not submersed in its binding cavities.

Keywords: Dehydropeptides; Enzyme inhibitors; Esterification; Molecular modeling.