Fluorogenic probes using 4-substituted-2-nitrobenzenesulfonyl derivatives as caging groups for the analysis of human glutathione transferase catalyzed reactions

Abstract

We have synthesized a series of 4-substituted-2-nitrobenzene-sulfonyl compounds for caged fluorogenic probes and conducted a Hammett plot analysis using the steady-state kinetic parameters. The results revealed that the glutathione transferase (GST) alpha catalyzed reaction was dependent on the σ value in the same way as the non-enzymatic reaction, whereas the dependence of the σ value of the GST mu and pi was not as pronounced as that of GST alpha.

Chemical Reactivity Window Determines Prodrug Efficiency toward Glutathione Transferase Overexpressing Cancer Cells

“…Having a less electron withdrawing acetyl group, as is also reflected in the difference of the nonenzymatic conversion rates (Figure 2C), ANS–DOX showed 10 to 30 times lower conversion rates for all enzymes compared to DNS–DOX as expected. 56 ANS–DOX was thus activated with a rate of 38.7 ± 0.2 nmol/min/mg by MGST1 and 493 ± 3 nmol/min/mg by GSTA1, whereas no activity could be measured for GSTP1 under the experimental conditions (Figure 2B). The presence of Triton X-100, furthermore, did not alter the ratio of nonenzymatic reactivity for the compounds drastically, suggesting that solubility and lipophilicity is not a major factor (Figure 2C).…”

A fluorophore's electron-deficiency does matter in designing high-performance near-infrared fluorescent probes

“…S6 †) showed HCy2 and HCy9 as the outstanding probes for potential practical applications in the following sections. This result overturns 4-cyano-2-nitrobenzenesulfonyl as the master key for all practical GST probes, although it was proved to be the most appropriate receptor unit for AcRh-based 8 and NI-based 13 probes.…”

“…[1][2][3][4][5] With little toxicity, high sensitivity, a fast and convenient detection process, and facile modication, more and more attention has been drawn to small molecule uorescent probes. [6][7][8][9][10][11][12] Recently, with the 1,8-naphthalimide (NI) scaffold, we have developed a two-photon uorescent probe NI3 for GSTs aer an elaborate investigation into the structure-activity relationships between nonenzymatic or enzymatic reactivities and the effective electrophilicity of the receptor unit. 13 Despite NI's two-photon absorptivity, its short emission wavelength impeded more practical applications such as in vivo imaging.…”

Fluorescent probes based on nucleophilic aromatic substitution reactions for reactive sulfur and selenium species: Recent progress, applications, and design strategies

“…Cleavage of the carbon-chalcogen bonds in phenyl-O ethers, phenyl-S ethers, and phenyl-Se ethers becomes increasingly facile as the atomic radius increases on going from oxygen to sulfur to selenium. In addition, the introduction of appropriate groups at different positions on the benzene ring can also modulate the ease of dissociation of phenyl ethers [153] , [154] , [155] .…”