Davies, Sarah published the artcileDevelopment of a self-immolative linker for tetrazine-triggered release of alcohols in cells, Quality Control of 100-70-9, the main research area is antibacterial drug triclosan prodrug preparation cycloocten tetrazine bond cleavage.
Bioorthogonal decaging reactions are a promising strategy for prodrug activation because they involve bond cleavage to release a mol. of interest. The trans-cyclooctene (TCO)-tetrazine inverse electron-demand Diels-Alder reaction has been widely applied in vivo for decaging of amine prodrugs, however, the release of alc.-containing bioactive compounds has been less well studied. Here, we report a TCO-carbamate benzyl ether self-immolative linker for the release of OH-mols. upon reaction with a tetrazine trigger. The benzyl ether linker proved to be highly stable and can rapidly liberate alcs. under physiol. conditions upon reaction with tetrazines. The mechanism and decaging yield were systematically examined by fluorescence and HPLC anal. by using a fluorogenic TCO-benzyl ether-coumarin probe and different 3,6-substituted tetrazine derivatives This study revealed that decaging occurs rapidly (t1/2 = 27 min) and the cycloaddition step happens within seconds (t1/2 = 7 s) with reaction rates of ≈100 M-1s-1. Importantly, the reaction is compatible with living organisms as demonstrated by the decaging of a prodrug of the antibacterial compound triclosan in the presence of live E. coli, that resulted in complete cell killing by action of the released “”OH-active drug””. Overall, this work describes a new linker for masking alc. functionality that can be rapidly reinstated through tetrazine-triggered decaging.
Organic & Biomolecular Chemistry published new progress about Antibacterial agents. 100-70-9 belongs to class nitriles-buliding-blocks, name is Picolinonitrile, and the molecular formula is C6H4N2, Quality Control of 100-70-9.
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts