Novel molecular photoswitches for use in chemical biology

光开关化合物可以通过光在两种异构体之间可逆地切换，它在利用光作为刺激的高时间和空间精度的广泛应用中继续吸引着人们的极大关注。最近建立的光药理学领域使用对特定细胞靶标（如受体或酶）具有选择性的光开关配体，并用作治疗实体。这些配体在光照射下发生形状、柔韧性或电子特性的变化，从而导致其对细胞靶标的亲和力发生变化；因此，它们表现出光依赖的治疗活性。偶氮杂芳烃是一种相对较新的但研究较少的光开关类型，其中传统的偶氮苯类的一个或两个芳基环被一个五元杂芳烃环所取代。在这个类别中，我们的小组最近发现了芳基唑，它提供了定量的光电开关和高热稳定性的Z异构体（半衰期可达1000天左右）。我们已经对一系列类似的偶氮杂芳基光开关的结构-性质关系有了很好的理解，现在正在探索这些最先进的光药理学应用系统。本提案将寻求开发光药理学制剂和改进设计的生物应用。一系列的目标将被探索，特别关注甲基转移酶。战略主题：医疗保健技术；物理科学研究领域：分析科学；物理科学：化学生物学和生物化学

Photoswitchable compounds, which can be reversibly switched between two isomers by light, continue to attract significant attention for a wide array of applications that capitalise on the high temporal and spatial precision of using light as a stimulus. The recently established field of photopharmacology uses photoswitchable ligands that are selective for a specific cellular target, such as a receptor or an enzyme, and are employed as therapeutic entities. These ligands undergo a change in shape, flexibility, or electronic properties upon irradiation with light that leads to a change in the affinity for their cellular target; therefore, they exhibit a light-dependent therapeutic activity. Azoheteroarenes represent a relatively new but understudied type of photoswitch, where one or both of the aryl rings from the conventional azobenzene class has been replaced with a five-membered heteroaromatic ring. Within this class, our group recently discovered the arylazopyrazoles, which offer quantitative photoswitching and high thermal stability of the Z isomer (half-lives of up to about 1000 days). We have developed excellent understanding of the structure-property relationships for a wide array of comparable azoheteroaryl photoswitches and are now placed to explore these state-of-the-art systems for photopharmacology applications. This proposal will seek to develop photopharmacological agents and improved designs for biological application. A range of targets will be explored, with a particular focus on methyltransferases.Strategic Themes: Healthcare Technologies; Physical SciencesResearch Areas: Analytical science; Physical Sciences: Chemical Biology and Biological Chemistry