核酸作为化学反应中的模板和催化剂：靶标引导的动态组合化学和原位点击化学以及 DNA/RNA 诱导的对映选择性反应,Chemical Society Reviews

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核酸作为化学反应中的模板和催化剂：靶标引导的动态组合化学和原位点击化学以及 DNA/RNA 诱导的对映选择性反应
Chemical Society Reviews ( IF 40.4 ) Pub Date : 2023-06-12 , DOI: 10.1039/d3cs00166k
Puja Saha ₁ , Deepanjan Panda ₁ , Jyotirmayee Dash ₁

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核酸在传递细胞信息和基因调控方面发挥着至关重要的作用。DNA 和 RNA 分子与多种人类疾病有关，因此为探索基于小分子的疗法提供了机会。然而，开发具有明确生物活性的目标选择性分子一直具有挑战性。在当前的情况下，世界不断爆发新的传染病，扩大化学工具集的范围以超越传统的药物发现策略来开发治疗相关的候选药物始终很重要。模板导向的合成方法已成为快速药物发现的有前途的工具。它允许生物靶标从反应片段池中选择或合成其配体。就地单击化学。尽管这些技术在二十年前才被发现，但已经证明了它们对于核酸靶标的有用性，治疗上重要的 DNA 和 RNA 靶标的应用数量不断增加就是例证。然而，与蛋白质靶标相比，核酸模板合成技术在药物发现中相对未经探索。在这篇综述文章中，我们对所有已报道的核酸模板合成研究进行了详细讨论，以描绘该策略在有效命中发现和先导化合物优化方面的巨大潜力。本文将通过对进展和新兴应用的总结来帮助扩大该策略的范围和实用性。此外，

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Nucleic acids as templates and catalysts in chemical reactions: target-guided dynamic combinatorial chemistry and in situ click chemistry and DNA/RNA induced enantioselective reactions

Nucleic acids play crucial roles in transferring cellular information and gene regulations. DNA and RNA molecules have been associated with multiple human diseases and thus offer opportunities for exploring small molecule-based therapeutics. However, developing target-selective molecules possessing well-defined biological activity, has always been challenging. In the current scenario, where the world is continuously experiencing outbreaks of new infectious diseases, it is always important to expand the scope of chemical toolsets to override conventional drug discovery strategies for developing therapeutically relevant drug candidates. The template-directed synthetic approach has emerged as a promising tool for rapid drug discovery. It allows a biological target to template the selection or synthesis of its ligands from a pool of reactive fragments. There are two main template-directed synthetic strategies: thermodynamically controlled dynamic combinatorial chemistry (DCC) and kinetically controlled target-guided in situ click chemistry. Though discovered only two decades ago, these techniques have proven their usefulness for nucleic acid targets, as exemplified by the increasing number of applications with therapeutically important DNA and RNA targets. However, nucleic acid templated synthetic techniques are relatively unexplored in drug discovery compared to protein targets. In this review article, we have presented a detailed discussion of all the reported nucleic acid templated synthetic studies to portray the great potential of this strategy for efficient hit discovery and lead optimisation. This article would assist in expanding the scope and utility of this strategy through a summary of the advancements and emerging applications. Additionally, a brief overview of the catalytic potential of nucleic acids in asymmetric synthesis has been provided to give a valuable vision of the use of nucleic acids to induce enantioselectivity in chiral drug-like candidates.

更新日期：2023-06-12

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