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Profiling system for skin kallikrein proteolysis applied in gene-deficient mouse models
Martin Horn1, Olga Zbodakova2, Petr Kasparek2,3
1Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Flemingovo n. 2, 166 10 Prague, Czech Republic.
Abstract:
Kallikrein-related proteases (KLKs) play a critical role in epidermis physiology and have been implicated in skin pathologies such as Netherton syndrome. The contribution of individual KLKs to skin proteolysis is poorly understood. Monitoring of their activities in skin proteome is hampered by overlapping substrate specificities, and there is a need for novel assays. Here, we present a platform of selective and sensitive fluorogenic substrates and inhibitors for profiling KLK5, KLK7 and KLK14. These chemical tools were evaluated using recombinant KLKs and tissue from a unique set of mice deficient in eight combinations of KLKs and their natural regulator LEKTI.
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