D-Luciferin, derivatives and analogues: synthesis and in vitro/in vivo luciferase-catalyzed bioluminescent activity

Abstract

D-luciferin is the natural substrate of all luciferases that catalyze the production of light in bioluminescent insects. The present review covers the synthesis of D-luciferin and derivatives or analogues that are substrates or inhibitors of the luciferase from the American firefly Photinus pyralis, the enzyme more frequently used in techniques of in vitro and optical imaging.

Bioluminescence: a versatile technique for imaging cellular and molecular features

“…A small, electron-donating group (e.g., -OH or NH 2 ) at this position is required for light production; 33 installing electron-withdrawing or bulky groups inhibits bioluminescence. 84,85 If the "cage" is labile to dened enzymatic activity, though, luciferin is released and available for the light emitting reaction. In these cases, light emission provides a direct readout on enzyme function.…”

“…Thus, modifying the luciferin core itself can result in altered emission spectra. 85,[156][157][158] In a recent example, Conley, et al synthesized a luciferin analogue comprising a selenium atom in place of sulfur (Fig. 5A).…”

2-(6-Bromobenzo[d]thiazol-2-yl)-5,5-dimethylthiazol-4(5H)-one

“…One prominent example of a bioluminescent organism is the firefly (Photinus pyralis), which employs the benzothiazole containing Luciferin for light emission (White et al, 1961). One known inhibitor for this Luciferin-Luciferase reaction is the structurally close related dimethyloxyluciferin (Meroni et al, 2009). This compound also shows a bright red fluorescence in the visible spectrum in the deprotonated state (Branchini et al, 2002).…”

“…For the chemi-and bioluminescence of firefly luciferin and related compounds, see: Jung et al (1975); White et al (1961White et al ( , 1979; Branchini et al (2002). For structural modifications of firefly luciferin, see: Meroni et al (2009); McCutcheon et al (2012); Branchini et al (2012); Wü rfel (2012). Luciferin and related structures are widely used in clinical and biochemical applications, see: Schä ffer (1987a,b); Kricka (1988); Josel et al (1994a,b); Shinde et al (2006).…”

Economical and scalable synthesis of 6-amino-2-cyanobenzothiazole

“…Functionalised 2-cyanobenzothiazoles (CBTs, 1 ) are key building blocks for the synthesis of luciferins 3 [1–3], substrates of natural and engineered firefly luciferases that are widely used for bioluminescence imaging (BLI) [4–5]. The typical preparation of luciferins 3 involves straightforward condensation of CBTs 1 with D-cysteine ( 2 ) (Scheme 1).…”