Design, synthesis, andin vitroevaluation of aza-peptide aldehydes and ketones as novel and selective protease inhibitors

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F20%3A00537297" target="_blank" >RIV/60077344:_____/20:00537297 - isvavai.cz</a>
Result on the web
<a href="https://www.tandfonline.com/doi/pdf/10.1080/14756366.2020.1781107?needAcces" target="_blank" >https://www.tandfonline.com/doi/pdf/10.1080/14756366.2020.1781107?needAcces</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1080/14756366.2020.1781107" target="_blank" >10.1080/14756366.2020.1781107</a>

Result language
angličtina
Original language name
Design, synthesis, andin vitroevaluation of aza-peptide aldehydes and ketones as novel and selective protease inhibitors
Original language description
Aza-peptide aldehydes and ketones are a new class of reversible protease inhibitors that are specific for the proteasome and clan CD cysteine proteases. We designed and synthesised aza-Leu derivatives that were specific for the chymotrypsin-like active site of the proteasome, aza-Asp derivatives that were effective inhibitors of caspases-3 and6, and aza-Asn derivatives that inhibitedS. mansoniandI. ricinuslegumains. The crystal structure of caspase-3 in complex with our caspase-specific aza-peptide methyl ketone inhibitor with an aza-Asp residue at P1 revealed a covalent linkage between the inhibitor carbonyl carbon and the active site cysteinyl sulphur. Aza-peptide aldehydes and ketones showed no cross-reactivity towards cathepsin B or chymotrypsin. The initialin vitroselectivity of these inhibitors makes them suitable candidates for further development into therapeutic agents to potentially treat multiple myeloma, neurodegenerative diseases, and parasitic infections.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10606 - Microbiology

Project
<a href="/en/project/EF16_019%2F0000759" target="_blank" >EF16_019/0000759: Centre for research of pathogenicity and virulence of parasites</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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