4-Oxo-β-lactams as Covalent Inhibitors of the Mitochondrial Intramembrane Protease PARL

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F24%3A00602835" target="_blank" >RIV/61388963:_____/24:00602835 - isvavai.cz</a>
Result on the web
<a href="https://doi.org/10.1021/acsmedchemlett.4c00384" target="_blank" >https://doi.org/10.1021/acsmedchemlett.4c00384</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acsmedchemlett.4c00384" target="_blank" >10.1021/acsmedchemlett.4c00384</a>

Result language
angličtina
Original language name
4-Oxo-β-lactams as Covalent Inhibitors of the Mitochondrial Intramembrane Protease PARL
Original language description
Rhomboid proteases play a variety of physiological roles, but rhomboid protease inhibitors have been mostly developed for the E. coli model rhomboid GlpG. In this work, we screened different electrophilic scaffolds against the human mitochondrial rhomboid PARL and found 4-oxo-β-lactams as submicromolar inhibitors. Multifaceted computations suggest explanations for the activity at the molecular scale and provide models of covalently bound complexes. Together with the straightforward synthesis of the 4-oxo-β-lactam scaffold, this may pave the way toward selective, nonpeptidic PARL inhibitors.
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
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OECD FORD branch
10608 - Biochemistry and molecular biology

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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