Viral proteases are indispensable for successful virion maturation, thus making them a prominent drug target. Their enzyme activity is tightly spatiotemporally regulated by expression in the precursor form with little or no activity, followed by activation via autoprocessing. These cleavage events are frequently triggered upon transportation to a specific compartment inside the host cell. Typically, precursor oligomerization or the presence of a co-factor is needed for activation. A detailed understanding of these mechanisms will allow ligands with non-canonical mechanisms of action to be designed, which would specifically modulate the initial irreversible steps of viral protease autoactivation. Binding sites exclusive to the precursor, including binding sites beyond the protease domain, can be exploited. Both inhibition and up-regulation of the proteolytic activity of viral proteases can be detrimental for the virus. All these possibilities are discussed using examples of medically relevant viruses including herpesviruses, adenoviruses, retroviruses, picornaviruses, caliciviruses, togaviruses, flaviviruses, and coronaviruses.
- MeSH
- antivirové látky farmakologie MeSH
- Flavivirus účinky léků metabolismus MeSH
- Herpesviridae účinky léků metabolismus MeSH
- HIV-1 účinky léků MeSH
- inhibitory virových proteáz farmakologie MeSH
- lidé MeSH
- lidské adenoviry účinky léků metabolismus MeSH
- SARS-CoV-2 účinky léků metabolismus MeSH
- virové nemoci farmakoterapie MeSH
- virové proteasy biosyntéza metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Inverse-electron-demand Diels-Alder (iEDDA) cycloaddition between 1,2,4,5-tetrazines and strained dienophiles belongs among the most popular bioconjugation reactions. In addition to its fast kinetics, this cycloaddition can be tailored to produce fluorescent products from non-fluorescent starting materials. Here we show that even the reaction intermediates formed in iEDDA cycloaddition can lead to the formation of new types of fluorophores. The influence of various substituents on their photophysical properties and the generality of the approach with use of various trans-cyclooctene derivatives were studied. Model bioimaging experiments demonstrate the application potential of fluorogenic iEDDA cycloaddition.
- MeSH
- cykloadiční reakce MeSH
- cyklooktany chemie MeSH
- fluorescenční barviva chemická syntéza chemie MeSH
- fluorescenční mikroskopie metody MeSH
- HeLa buňky MeSH
- heterocyklické sloučeniny bicyklické chemická syntéza chemie MeSH
- heterocyklické sloučeniny monocyklické chemie MeSH
- konfokální mikroskopie metody MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH