Introducing New Inhibitors for Kallikrein-related peptidase 6 (KLK6)

Introduction and Objectives: The human Kallikrein-related peptidase 6 (KLK6) gene belongs to the 15-member Kallikrein gene family mapping to chromosome 19q13.3. Encoding for an enzyme with trypsin-like properties. The observed highly upregulated expression in various cancers, neurodegenerative diseases and skin conditions has led to the discovery that KLK6 participates in other cellular pathways including inflammation, receptor activation and regulation of apoptosis. KLK6 can degrade components of the extracellular matrix and increased activity promotes cancer invasion and metastasis. This characteristic suggests KLK6 as an attractive target for therapeutic interventions. However, inhibitors that specifically target KLK6 have not yet been reported, possibly because KLK6 shares a high sequence homology and structural similarity with other serine proteases and resists inhibition by many polypeptide inhibitors. The purpose of this study was to design and engineering a novel inhibitor for KLK6.Material and Method: In this study, first, the inhibitors were designed and investigated by using bioinformatics and molecular modeling. At this moment, the in vitro phase is being performed. In this phase, the KLK6 enzyme and a variety of engineered inhibitors will first be cloned, expressed and purified. Next, the activity of the KLK6 enzyme in the presence of inhibitors with the aid of a fluorogenic substrate will be investigated.Result: The new inhibitor, by forming more effective bonds, we hope that it will be able to inhibit the KLK6 enzyme in a stronger and more stable manner.Conclusion: In summary, Given the important role of KLK6 in a variety of cancers and chronic inflammatory diseases, we hope that the new inhibitor can be of help in treating these diseases. Of course, this needs further study.

کلیدواژه ها:

Kallikrein6 ، Cancer ، Inflammatory Diseases ، Inhibitor