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Open AccessArticle

Inhibition of Human Cathepsins B and L by Caffeic Acid and Its Derivatives

Department of Chemistry and Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, 1000 Ljubljana, Slovenia
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Biomolecules 2021, 11(1), 31; https://doi.org/10.3390/biom11010031
Received: 30 November 2020 / Revised: 18 December 2020 / Accepted: 25 December 2020 / Published: 29 December 2020
Caffeic acid (CA) and its derivatives caffeic acid phenethyl ester (CAPE) and chlorogenic acid (CGA) are phenolic compounds of plant origin with a wide range of biological activities. Here, we identify and characterize their inhibitory properties against human cathepsins B and L, potent, ubiquitously expressed cysteine peptidases involved in protein turnover and homeostasis, as well as pathological conditions, such as cancer. We show that CAPE and CGA inhibit both peptidases, while CA shows a preference for cathepsin B, resulting in the strongest inhibition among these combinations. All compounds are linear (complete) inhibitors acting via mixed or catalytic mechanisms. Cathepsin B is more strongly inhibited at pH 7.4 than at 5.5, and CA inhibits its endopeptidase activity preferentially over its peptidyl-dipeptidase activity. Altogether, the results identify the CA scaffold as a promising candidate for the development of cathepsin B inhibitors, specifically targeting its endopeptidase activity associated with pathological proteolysis of extracellular substrates. View Full-Text
Keywords: enzyme inhibition; proteolysis; peptidase; catalytic inhibition; mixed inhibition; chlorogenic acid; caffeic acid phenethyl ester enzyme inhibition; proteolysis; peptidase; catalytic inhibition; mixed inhibition; chlorogenic acid; caffeic acid phenethyl ester
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MDPI and ACS Style

Ulčakar, L.; Novinec, M. Inhibition of Human Cathepsins B and L by Caffeic Acid and Its Derivatives. Biomolecules 2021, 11, 31. https://doi.org/10.3390/biom11010031

AMA Style

Ulčakar L, Novinec M. Inhibition of Human Cathepsins B and L by Caffeic Acid and Its Derivatives. Biomolecules. 2021; 11(1):31. https://doi.org/10.3390/biom11010031

Chicago/Turabian Style

Ulčakar, Liza; Novinec, Marko. 2021. "Inhibition of Human Cathepsins B and L by Caffeic Acid and Its Derivatives" Biomolecules 11, no. 1: 31. https://doi.org/10.3390/biom11010031

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