Genetically Encoded Chemical Decaging in Living Bacteria

We report the genetically encoded chemical decaging strategy for protein activation in living bacterial cells. In contrast to the metabolically labile photocaging groups inside <i>Escherichia coli</i>, our chemical decaging strategy that relies on the inverse electron-demand Diels–Alder (iDA) reaction is compatible with the intracellular environment of bacteria, which can be a general tool for gain-of-function study of a given protein in prokaryotic systems. By applying this strategy for <i>in situ</i> activation of the indole-producing enzyme TnaA, we built an orthogonal and chemically inducible indole production pathway inside <i>E. coli</i> cells, which revealed the role of indole in bacterial antibiotic tolerance

Genetically Encoded Chemical Decaging in Living Bacteria

We report the genetically encoded chemical decaging strategy for protein activation in living bacterial cells. In contrast to the metabolically labile photocaging groups inside <i>Escherichia coli</i>, our chemical decaging strategy that relies on the inverse electron-demand Diels–Alder (iDA) reaction is compatible with the intracellular environment of bacteria, which can be a general tool for gain-of-function study of a given protein in prokaryotic systems. By applying this strategy for <i>in situ</i> activation of the indole-producing enzyme TnaA, we built an orthogonal and chemically inducible indole production pathway inside <i>E. coli</i> cells, which revealed the role of indole in bacterial antibiotic tolerance

Design, Synthesis, and Evaluation of Tetrahydropyrrolo[1,2‑<i>c</i>]pyrimidines as Capsid Assembly Inhibitors for HBV Treatment

The discovery of novel tetrahydropyrrolo­[1,2-<i>c</i>]­pyrimidines derivatives from <b>Bay41_4109</b> as hepatitis B virus (HBV) inhibitors is herein reported. The structure–activity relationship optimization led to one highly efficacious compound <b>28a</b> (IC₅₀ = 10 nM) with good PK profiles and the favorite L/P ratio. The hydrodynamic injection model in mice clearly demonstrated the efficacy of <b>28a</b> against HBV replication