Department of Engineering Science, Graduate School of Informatics and Engineering,, The University of Electro-Communications, Chofu, Japan.
Center for Neuroscience and Biomedical Engineering, The University of Electro-Communications, Chofu, Japan.
Chirality. 2020 Jul;32(7):922-931. doi: 10.1002/chir.23236. Epub 2020 May 4.
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 (λ = 705 nm) and mutant luciferase AlaLuc (λ = 655 nm).
有趣的是，只有 D 型萤火虫荧光素通过荧光素酶-荧光素（L-L）反应产生光。某些结构修饰的萤火虫荧光素类似物具有生物发光（BL）活性；然而，所有 L 型荧光素类似物均无 BL 活性。迄今为止，我们小组已经开发出具有中等 BL 活性的荧光素类似物，它们可以产生各种波长的光。对于体内生物发光成像，检测灵敏度的一个重要因素是 L-L 反应发射的光子数量的组织通透性，并且近红外（NIR）范围（700-900nm）的光的波长最适合该目的。我们开发的一些 NIR 荧光素类似物可用于体内实验，使得能够以高灵敏度从小鼠的深部靶组织中检测到光子，而只有少数 NIR 荧光素类似物可以通过野生型荧光素酶和/或突变型荧光素酶的 L-L 反应产生 NIR 光。基于构效关系，我们在此设计并合成了一种具有 5-烯丙基-6-二甲基氨基-2-萘基乙烯基部分的荧光素类似物。该类似物与野生型荧光素酶（λ=705nm）和突变型荧光素酶 AlaLuc（λ=655nm）均表现出 NIR BL 发射。
