Coelenterazine analogues emit red-shifted bioluminescence with NanoLuc. Issue 40 (3rd October 2017)

• Record Type: Journal Article
• Authors: Shakhmin, Anton; Hall, Mary P.; Machleidt, Thomas; Walker, Joel R.; Wood, Keith V.; Kirkland, Thomas A.
• Is Part Of: Organic & biomolecular chemistry. Volume 15:Issue 40(2017)
• Page Start: 8559
• Page End: 8567
• Publication Date: 2017-10-03
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c7ob01985h
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : Synthesis and biological investigation of coelenterazine analogs that demonstrate a tunable red-shift in their bioluminescent emission with NanoLuc luciferase. Abstract : We report the synthesis and characterization of novel coelenterazine analogues that demonstrate a red-shift in their bioluminescent emission with NanoLuc luciferase. These coelenterazines can be tuned to shift the bioluminescent emission from blue light in the native system. In particular, direct attachment of an aryl moiety to the imidazopyrazinone core of furimazine at the C8 position provides a significant red-shift while maintaining reasonable light output. In addition, modification of the C6 aryl moiety provided additive red-shifts, and by combining the most promising modifications we report a coelenterazine with a maximum emission near 600 nm with NanoLuc. Finally, we show that this new bioluminescent system is capable of efficient BRET to far-red fluorophores. We anticipate these new principles of NanoLuc substrate design will impact applications that depend on shifting the colour of emission to the red, most notably in vivo bioluminescent imaging.