Development of near‐infrared firefly luciferin analogue reacted with wild‐type and mutant luciferases

• Published in: Chirality (New York, N.Y.) N.Y.), 2020-07, Vol.32 (7), p.922-931
• Main Authors: Kitada, Nobuo, Saito, Ryohei, Obata, Rika, Iwano, Satoshi, Karube, Kazuma, Miyawaki, Atsushi, Hirano, Takashi, Maki, Shojiro A.
• Format: Article
• Language: English
• Subjects: Akaluc; Analogs; Animal tissues; Animals; Bioluminescence; Fireflies; Firefly Luciferin - analogs & derivatives; Firefly Luciferin - chemistry; Infrared radiation; Luciferases - chemistry; Luciferases - metabolism; Luciferin; luciferin analogues; luciferin‐luciferase reaction; Luminescent Measurements - methods; Mice; mutant luciferase; Mutants; near‐infrared bioluminescence; Permeability; Photinus pyralis luciferase; Photons; Sensitivity; Special Issue; Special Issue: In Honor and Memory of Prof. Koji Nakanishi; Stereoisomerism; Structure-Activity Relationship; Target detection; TokeOni; Wavelengths
• ISSN: 0899-0042; 1520-636X
• DOI: 10.1002/chir.23236

Interestingly, only the D‐form of firefly luciferin produces light by luciferin–luciferase (L–L) reaction. Certain firefly luciferin analogues with modified structures maintain bioluminescence (BL) activity; however, all L‐form luciferin analogues show no BL activity. To this date, our group has developed luciferin analogues with moderate BL activity that produce light of various wavelengths. For in vivo bioluminescence imaging, one of the important factors for detection sensitivity is tissue permeability of the number of photons emitted by L–L reaction, and the wavelengths of light in the near‐infrared (NIR) range (700–900 nm) are most appropriate for the purpose. Some NIR luciferin analogues by us had performance for in vivo experiments to make it possible to detect photons from deep target tissues in mice with high sensitivity, whereas only a few of them can produce NIR light by the L–L reactions with wild‐type luciferase and/or mutant luciferase. Based on the structure–activity relationships, we designed and synthesized here a luciferin analogue with the 5‐allyl‐6‐dimethylamino‐2‐naphthylethenyl moiety. This analogue exhibited NIR BL emissions with wild‐type luciferase (λmax = 705 nm) and mutant luciferase AlaLuc (λmax = 655 nm).