Ramos-Soriano Javier, Galan M Carmen
School of Chemistry, University of Bristol, Cantock's Close, Bristol BS8 1TS, United Kingdom.
JACS Au. 2021 Sep 7;1(10):1516-1526. doi: 10.1021/jacsau.1c00283. eCollection 2021 Oct 25.
G-quadruplex (G4) oligonucleotide secondary structures have recently attracted significant attention as therapeutic targets owing to their occurrence in human oncogene promoter sequences and the genome of pathogenic organisms. G4s also demonstrate interesting catalytic activities in their own right, as well as the ability to act as scaffolds for the development of DNA-based materials and nanodevices. Owing to this diverse range of opportunities to exploit G4 in a variety of applications, several strategies to control G4 structure and function have emerged. Interrogating the role of G4s in biology requires the delivery of small-molecule ligands that promote its formation under physiological conditions, while exploiting G4 in the development of responsive nanodevices is normally achieved by the addition and sequestration of the metal ions required for the stabilization of the folded structure. Although these strategies prove successful, neither allows the system in question to be controlled externally. Meanwhile, light has proven to be an attractive means for the control of DNA-based systems as it is noninvasive, can be delivered with high spatiotemporal precision, and is orthogonal to many chemical and biological processes. A plethora of photoresponsive DNA systems have been reported to date; however, the vast majority deploy photoreactive moieties to control the stability and assembly of duplex DNA hybrids. Despite the unique opportunities afforded by the regulation of G-quadruplex formation in biology, catalysis, and nanotechnology, comparatively little attention has been devoted to the design of photoresponsive G4-based systems. In this Perspective, we consider the potential of photoresponsive G4 assemblies and examine the strategies that may be used to engineer these systems toward a variety of applications. Through an overview of the main developments in the field to date, we highlight recent progress made toward this exciting goal and the emerging opportunities that remain ripe for further exploration in the coming years.
G-四链体（G4）寡核苷酸二级结构最近作为治疗靶点引起了广泛关注，因为它们存在于人类癌基因启动子序列和致病生物体的基因组中。G4本身还表现出有趣的催化活性，以及作为基于DNA的材料和纳米器件开发支架的能力。由于在各种应用中利用G4有如此广泛的机会，已经出现了几种控制G4结构和功能的策略。探究G4在生物学中的作用需要递送在生理条件下促进其形成的小分子配体，而在响应性纳米器件的开发中利用G4通常是通过添加和螯合稳定折叠结构所需的金属离子来实现的。尽管这些策略证明是成功的，但都不能使所讨论的系统受到外部控制。同时，光已被证明是控制基于DNA的系统的一种有吸引力的手段，因为它是非侵入性的，可以以高时空精度递送，并且与许多化学和生物过程正交。迄今为止，已经报道了大量的光响应性DNA系统；然而，绝大多数系统都部署了光反应性部分来控制双链DNA杂交体的稳定性和组装。尽管在生物学、催化和纳米技术中调节G-四链体形成提供了独特的机会，但对基于光响应性G4的系统设计的关注相对较少。在这篇综述中，我们考虑了光响应性G4组装体的潜力，并研究了可用于设计这些系统以实现各种应用的策略。通过概述该领域迄今为止的主要进展，我们强调了朝着这一令人兴奋的目标取得的最新进展以及未来几年仍有待进一步探索的新出现的机会。
