Inhibition of Thiol‐Mediated Uptake with Irreversible Covalent Inhibitors
| Autor: | Yangyang Cheng, Takehiro Kato, Jerome Waser, Bumhee Lim, Naomi Sakai, Abhaya Kumar Mishra, Eliott Le Du, Elija Grinhagena, Dimitri Moreau, Stefan Matile, Anh Tuan Pham |
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| Jazyk: | angličtina |
| Předmět: |
General interest
nosyl protecting group 010402 general chemistry 01 natural sciences Biochemistry Catalysis Inorganic Chemistry Molecular recognition antiviral agents inhibitors Drug Discovery hypervalent iodine reagents Reactivity (chemistry) Physical and Theoretical Chemistry Protecting group thiol-mediated uptake chemistry.chemical_classification 010405 organic chemistry Chemistry Organic Chemistry Hypervalent molecule TRPA1 pain receptor hypervalent compounds Combinatorial chemistry 0104 chemical sciences 3. Good health Covalent bond Reagent ddc:540 Thiol |
| Zdroj: | Helvetica Chimica Acta, Vol. 104, No e2100085 (2021) pp. 1-9 Helvetica Chimica Acta |
| ISSN: | 1522-2675 0018-019X |
| DOI: | 10.1002/hlca.202100085 |
| Popis: | Thiol-mediated uptake is emerging as method of choice to penetrate cells. This study focuses on irreversible covalent inhibitors of thiol-mediated uptake. High-content high-throughput screening of the so far largest collection of hypervalent iodine reagents affords inhibitors that are more than 250 times more active than Ellman’s reagent and rival the best dynamic covalent inhibitors. Comparison with other irreversible reagents reveals that inhibition within one series follows reactivity, whereas inhibition across series deviates from reactivity. These trends support that molecular recognition, besides dynamic covalent exchange, contributes significantly to thiol-mediated uptake. The most powerful inhibitors besides the best hypervalent iodine reagents were Fukuyama’s nosyl protecting group and super-cinnamaldehydes that have been introduced as irreversible activators of the pain receptor TRPA1. Considering that several viruses use different forms of thiol-mediated uptake to enter cells, the identification of new irreversible inhibitors of thiol-mediated uptake is of general interest for the discovery of new antivirals. |
| Databáze: | OpenAIRE |
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