Jiménez M Consuelo, Miranda Miguel A
Departamento de Quimica/Instituto de Tecnologia Quimica UPV-CSIC. Universitat Politecnica de Valencia, Camino de Vera s/n, Apdo 22012, E-46071 Valencia, Spain.
Curr Top Med Chem. 2014;14(23):2734-42. doi: 10.2174/1568026614666141216100907.
The properties of triplet excited states are markedly medium-dependent, which turns this species into valuable tools for investigating the microenvironments existing in protein binding pockets. Monitoring of the triplet excited state behavior of drugs within transport proteins (serum albumins and α1-acid glycoproteins) by laser flash photolysis constitutes a valuable source of information on the strength of interaction, conformational freedom and protection from oxygen or other external quenchers. With proteins, formation of spatially confined triplet excited states is favored over competitive processes affording ionic species. Remarkably, under aerobic atmosphere, the triplet decay of drug@protein complexes is dramatically longer than in bulk solution. This offers a convenient dynamic range for assignment of different triplet populations or for stereochemical discrimination. In this review, selected examples of the application of the laser flash photolysis technique are described, including drug distribution between the bulk solution and the protein cavities, or between two types of proteins, detection of drug-drug interactions inside proteins, and enzyme-like activity processes mediated by proteins. Finally, protein encapsulation can also modify the photoreactivity of the guest. This is illustrated by presenting an example of retarded photooxidation.
三重激发态的性质显著依赖于介质，这使得该物种成为研究蛋白质结合口袋中微环境的有价值工具。通过激光闪光光解监测药物在转运蛋白（血清白蛋白和α1-酸性糖蛋白）中的三重激发态行为，构成了关于相互作用强度、构象自由度以及免受氧气或其他外部猝灭剂影响的有价值信息来源。对于蛋白质而言，形成空间受限的三重激发态比产生离子物种的竞争过程更受青睐。值得注意的是，在有氧气氛下，药物@蛋白质复合物的三重态衰变比在本体溶液中长得多。这为区分不同的三重态群体或进行立体化学鉴别提供了便利的动态范围。在本综述中，描述了激光闪光光解技术应用的选定示例，包括药物在本体溶液和蛋白质腔之间或两种蛋白质类型之间的分布、蛋白质内部药物-药物相互作用的检测以及蛋白质介导的类酶活性过程。最后，蛋白质包封也可以改变客体的光反应性。通过给出一个光氧化延迟的例子来说明这一点。
