Inhibition of human cathepsins B and L by caffeic acid and its derivatives

Ulčakar, Liza (avtor), Novinec, Marko (avtor)

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.

• Jezik: Angleški jezik
• Ključne besede: enzyme inhibition, proteolysis, peptidase, catalytic inhibition, mixed inhibition, chlorogenic acid, caffeic acid phenethyl ester
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FKKT - Fakulteta za kemijo in kemijsko tehnologijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2021
• Št. strani: 9 str.
• Številčenje: Vol. 11, iss. 1, art. 31
• PID: 20.500.12556/RUL-134780
• UDK: 577.15
• ISSN pri članku: 2218-273X
• DOI: 10.3390/biom11010031
• COBISS.SI-ID: 45685763
• Datum objave v RUL: 01.02.2022

Gradivo je del revije

• Naslov: Biomolecules
• Skrajšan naslov: Biomolecules
• Založnik: MDPI
• ISSN: 2218-273X
• COBISS.SI-ID: 519952921

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
• Začetek licenciranja: 01.01.2021

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: inhibicija encimov, proteoliza, peptidaza, katalitična inhibicija, mešana inhibicija, klorogenska kislina, fenetilni ester kavne kisline

Projekti

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: P1-0140
• Naslov: Proteoliza in njena regulacija