Abstract
The firefly bioluminescence reaction has been exploited for in vivo optical imaging in life sciences. To develop highly sensitive bioluminescence imaging technology, many researchers have synthesized luciferin analogs and luciferase mutants. This chapter first discusses synthetic luciferin analogs and their structure–activity relationships at the luminescence wavelength of the firefly bioluminescence reaction. We then discuss the development of luciferin analogs that produce near-infrared (NIR) light. Since NIR light is highly permeable for biological tissues, NIR luciferin analogs might sensitively detect signals from deep biological tissues such as the brain and lungs. Finally, we introduce two NIR luciferin analogs (TokeOni and seMpai) and a newly developed bioluminescence imaging system (AkaBLI). TokeOni can detect single-cell signals in mouse tissue and luminescence signals from marmoset brain, whereas seMpai can detect breast cancer micro-metastasis. Both reagents are valid for in vivo bioluminescence imaging with high sensitivity.
Highlights
This chapter focuses on synthetic substrates of firefly luciferase, which are employed in firefly bioluminescence imaging (BLI)
By studying the structure–activity relationships of these analogs and Photinus pyralis (Ppy) luciferase, we have developed luciferin analogs that produce wide-spectrum light, along with NIR luciferin analogs (AkaLumine, TokeOni, seMpai) for BLI
Analogs of 1 were first synthesized by White et al in 1966. They showed that aminoluciferin (2, Figure 1), in which the hydroxyl group of benzothiazole is replaced with an amino group, can function as a substrate of firefly luciferase (Fluc) and emit red bioluminescence [25]
Summary
In Japan, watching the light of fireflies has been a summer tradition for over one thousand years. This chapter focuses on synthetic substrates of firefly luciferase, which are employed in firefly bioluminescence imaging (BLI). BLI technology has observed biological events in vivo [2–8]. Our group has developed firefly substrate analogs for use in these research fields. The firefly bioluminescence reaction proceeds via the oxidation of d-luciferin (1, LH2, Figure 1) catalyzed by firefly luciferase (Fluc) in the presence of adenosine triphosphate (ATP), Mg2+ and O2 by a two-step reaction. Yellow-green light is not able to penetrate biological tissues [20], and is useful only for imaging shallow tissues such as subcutaneous tissues. By studying the structure–activity relationships of these analogs and Photinus pyralis (Ppy) luciferase, we have developed luciferin analogs that produce wide-spectrum light (from blue to red), along with NIR luciferin analogs (AkaLumine, TokeOni, seMpai) for BLI.
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