Liza Ulčakar (Author), Marko Novinec (Author)

Abstract

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.

Keywords

inhibicija encimov;proteoliza;peptidaza;katalitična inhibicija;mešana inhibicija;klorogenska kislina;fenetilni ester kavne kisline;enzyme inhibition;proteolysis;peptidase;catalytic inhibition;mixed inhibition;chlorogenic acid;caffeic acid phenethyl ester;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: UL FKKT - Faculty of Chemistry and Chemical Technology
UDC: 577.15
COBISS: 45685763 Link will open in a new window
ISSN: 2218-273X
Views: 180
Downloads: 62
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Other data

Secondary language: Slovenian
Secondary keywords: inhibicija encimov;proteoliza;peptidaza;katalitična inhibicija;mešana inhibicija;klorogenska kislina;fenetilni ester kavne kisline;
Type (COBISS): Article
Pages: str. 1-9
Volume: ǂVol. ǂ11
Issue: ǂiss. ǂ1
Chronology: Jan. 2021
DOI: 10.3390/biom11010031
ID: 14418268