Red‐Shifted Bioluminescence Using Substrate‐Fluorophore Conjugates

Article Article scientifique Article Red‐Shifted Bioluminescence Using Substrate‐Fluorophore Conjugates eng 2024-12-17 2025-01 author Narbonne Clément Maël Department of Organic Chemistry Faculty of Sciences University of Geneva 1211 Geneva Switzerland 419511 Chimie organique (groupe 5) (CHOR5) author Laxio Arenas Jose Antonio Manuel Department of Organic Chemistry Faculty of Sciences University of Geneva 1211 Geneva Switzerland 984006 author Russo Francesco Department of Organic Chemistry Faculty of Sciences University of Geneva 1211 Geneva Switzerland 956582 Chimie organique (groupe 5) (CHOR5) author Winssinger Nicolas 0000-0003-1636-7766 Department of Organic Chemistry Faculty of Sciences University of Geneva 1211 Geneva Switzerland 769664 Département de chimie organique (CHIOR) e202400156 10.1002/hlca.202400156 0018-019X https://onlinelibrary.wiley.com/doi/10.1002/hlca.202400156 NanoLuc (NLuc) is one of the brightest luciferases and has been used in numerous reporter assays and sensor designs. However, its blue light emission (460 nm) is suboptimal for deep tissue imaging or some diagnostic application, and red shifting its emission is desirable. Here, we report the design and synthesis of novel furimazine and coelenterazine analogs conjugated with fluorophores to achieve red‐shifted bioluminescence with NLuc and closely related H‐Luc via a bioluminescence resonance energy transfer (BRET). Structural insights into NLuc‐substrate interactions informed the functionalization of substrates. We report the synthesis of novel substrate‐fluorophore conjugates. We show that red‐shifted emission was achieved with high BRET ratios. The conjugates are less bright than the parent substrates, but our study highlights the importance of linker length and flexibility for optimizing bioluminescence emission reaching wavelength beyond 600 nm. Dewey 540 Swiss National Science Foundation Encoding and programing chemical biocircuitry 219316 CH Projects 36 Département de chimie organique 141 false 762 Groupe Winssinger Helvetica chimica acta 108 1 b8c5d4a9-aefc-4772-91c1-b02efc321d8f Article (Published version) Restricted file.pdf 12093984 application/pdf 6ef8c54d6253956410a383e23a7261bff32f3b827bee7f882f669a6a5ad898aa restrictedAccess Faculté des sciences / Section de chimie et biochimie / Département de chimie organique

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Red‐Shifted Bioluminescence Using Substrate‐Fluorophore Conjugates	Helvetica chimica acta			2025	40	0

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Laxio Arenas, Jose Antonio Manuel