Novel furimazine derivatives for nanoluciferase bioluminescence with various C-6 and C-8 substituents

Abstract

Nano luciferase (NLuc) is the emerging commercially available luciferase considering its small size and superior bioluminescence performance. Nevertheless, this bioluminescence system has some limitations, including narrow emission wavelength and conserved...

Brightening up Biology: Advances in Luciferase Systems for in Vivo Imaging

“… 39 Recent studies and overviews covering the progress of the chemical synthesis and structure–activity studies of CTZ analogs exist for interested readers. 37 , 40 − 43 …”

“…Substitution at the C-2, C-5, C-6, and C-8 positions of the imidazopyrazinone core has yielded enhancements in bioluminescence properties, with changes at the C-2 position modifying the reaction rate and the C-6/C-8 positions influencing the emission spectra. , One notable CTZ analog developed by Promega Corporation, ViviRen, exhibited up to a 10-fold higher signal in vivo than CTZ when paired with RLuc, while showing reduced autoluminescence . Recent studies and overviews covering the progress of the chemical synthesis and structure–activity studies of CTZ analogs exist for interested readers. ,− …”

Comparative Investigation of the Chemiluminescent Properties of a Dibrominated Coelenterazine Analog

“…One of the most studied CL/BL substrates is Coelenterazine (Clz, Scheme 1 ) [ 1 , 3 , 16 , 17 , 18 , 19 , 20 , 21 ], which is present in many marine BL organisms [ 22 ]. Clz is capable of both BL (with luciferase enzymes or photoproteins) [ 3 ] and CL (triggered without an enzyme/protein by oxygenation) [ 23 , 24 , 25 ]. These Clz-based reactions follow a mechanism that consists in two steps: first, there is the oxygenation of the imidazopyrazinone core that leads to the formation of dioxetanone, the high-energy peroxide intermediate; the dioxetanone will undergo thermolysis almost instantly due to its high instability, during which the reacting molecules can cross directly to singlet excited states, resulting in the chemiexcited light emitter coelenteramide [ 1 , 3 , 4 , 20 ].…”

“…Two of the most well-known examples are Coelenterazine 400a (Clz400a, Scheme 1 ) and Coelenterazine-e (Clz-e, Scheme 1 ). Clz400a generates light with an emission maximum at ~400 nm, and it is generally used for bioluminescence resonance energy transfer (BRET) in the presence of Renilla luciferase due its minimal interference with the emission of fluorescent acceptors [ 25 , 26 ]. As for Clz-e, it possesses an additional ethyl group to Clz, which forms an additional ring system.…”

“…It should be noted that besides the already commercialized Clz-based analogs (such as Clz400a and Clz-e), there has been made a significant effort by the research community to develop new Clz-based molecules with enhanced properties, such as brighter light-emission, red-shifted emission, and longer emission half-life [ 19 , 21 , 25 , 26 , 28 , 29 , 30 , 31 , 32 , 33 ]. This results from the increasing usefulness of both the BL and CL reactions of Clz and related imidazopyrazinones, in different fields, such as bioimaging [ 6 , 34 , 35 , 36 ] and sensing [ 33 , 37 , 38 ].…”