Development of Inhibitors for Human Tissue Kallikreins

Abstract

Protease inhibitors can directly or indirectly affect the active proteolytic enzyme, limiting or eliminating their ability to catalyze the cleavage of peptide bonds. These molecules may also act selectively or specifically, endogenously controlling various physiological processes. In recent years our group has been working on developing inhibitors for proteases, particularly against human tissue kallikreins (KLKs), which comprise a family of 15 serine proteases distributed in various tissues of the human body. They appear involved in several pathological events and therefore it is believed that specific inhibitors to these enzymes may represent new therapeutic procedures for certain pathologies. The KLKs also appear differentially expressed in cancer, and for this reason they are pointed as potential biomarkers for this kind of pathology. The most representative case is the human tissue kallikrein 3 (KLK3), which is also called PSA. Thus in this project we are proposing new strategies for the development of inhibitors for the KLKs, but that may also be used for any other proteolytic enzyme. Here we will work with three different strategies based in synthetic inhibitors, protein inhibitors, and the recombinant antibodies. (AU)