Engineering of an archaeal phosphodiesterase to trigger aggregation-induced emission (AIE) of synthetic substrates

Abstract

Aggregation-induced emission (AIE) probes that can be triggered by enzymatic activity are valuable for applications across the life sciences.

Indoxyl-glucosides bearing tethers for enzymatically triggered cross-linking

“…The reaction mixture was diluted with ethyl acetate (6 mL), washed [aqueous HCl (1 M, 6 mL) and brine (6 mL)], dried (Na 2 SO 4 ), and filtered. The filtrate was concentrated and chromatographed [silica, CH 2 Cl 2 /acetone (5 : 1)] to afford a white foam (210 mg, 46%): 1 (10). A sample of pyridine (34 mL, 0.43 mmol) was added to a suspension of 7 (156 mg, 0.21 mmol), 4-nitrophenyl chloroformate (V, 64 mg, 0.32 mmol), and activated molecular sieves 4 Å (500 mg) in CH 2 Cl 2 (8.5 mL).…”

“…One possible application of the latter is molecular brachytherapy, where a radionuclide-containing compound undergoes assembly into an immobile precipitate upon enzymatic action. Such a method, while far from realization, [6][7][8][9][10][11][12][13][14][15][16][17] would complement present-day brachytherapy, 18,19 wherein a radionuclide-containing object of macroscopic scale (e.g., pin or bead or wire) is surgically implanted in tissue. Numerous cancerous tissues are known to contain elevated levels of enzymes.…”

Tailoring the AIE Chromogen 2-(2-Hydroxyphenyl)benzothiazole for Use in Enzyme-Triggered Molecular Brachytherapy

“…Blocking the hydroxy group by phosphorylation, as shown for III-IX, can trap HBT unit in the enol form and prohibit the ESIPT process. (Figure 3) [29,32,34,35]. E matic cleavage of the phosphoryl group unveils the hydroxy group, and the HBT uni undergo ESIPT with accompanying emission, typically in the green region (Figure 4) Blocking the hydroxy group by phosphorylation, as shown for III-IX, can trap the HBT unit in the enol form and prohibit the ESIPT process.…”

“…E matic cleavage of the phosphoryl group unveils the hydroxy group, and the HBT uni undergo ESIPT with accompanying emission, typically in the green region (Figure 4) Blocking the hydroxy group by phosphorylation, as shown for III-IX, can trap the HBT unit in the enol form and prohibit the ESIPT process. (Figure 3) [29,32,34,35]. Enzymatic cleavage of the phosphoryl group unveils the hydroxy group, and the HBT unit can undergo ESIPT with accompanying emission, typically in the green region (Figure 4).…”

“…The development of targeted strategies requires focus on multiple, rather independent components. Recently, we engineered a non-native, archaeal phosphodiesterase to trigger the cleavage of a benzothiazole-phosphodiester to release the benzothiazole under conditions wherein a phosphatase was comparatively inactive [29]. In this paper, we focus on chemistry of the benzothiazole unit.…”