从简单给药到多模态系统:大分子平台在生物正交药物合成中的关键作用。

Tieze van den Elsen, Kevin Neumann
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引用次数: 0

摘要

靶向给药策略已成为克服传统挑战(如生物利用度差和与传统给药方法相关的副作用)的有希望的解决方案。在这些策略中,前药的使用提供了一种可行的方法,通过利用体内酶或受控的化学转化来提高药物的疗效和特异性。生物正交化学的出现彻底改变了前药激活,提供了超越传统方法的多种激活策略。这篇综述探讨了生物正交化学,特别是过渡金属催化,与前药激活策略的整合,重点是利用大分子支架作为平台,在生物环境中实现和定位这些化学反应。具体地说,本文综述了过渡金属催化剂介导的原位成键合成的发展领域,通常是通过使用大分子平台来实现的。通过在分子内或分子间形成碳-碳或碳杂原子键,这种方法比传统的解封策略具有优势,因为前药中没有药物活性基序。我们强调大分子平台在将生物正交化学整合到多模态系统中的核心作用,这些系统可以实现靶向策略和刺激反应行为,这对于实现位点特异性激活和最小化脱靶效应至关重要。我们得出结论,这一领域的未来取决于反合成前药设计的发展,以及多模块大分子平台的使用和发展,以容纳和实现新的生物正交过渡金属催化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
From simple delivery to multimodal systems: the critical role of macromolecular platforms in bioorthogonal drug synthesis.

Targeted drug delivery strategies have emerged as promising solutions to overcome traditional challenges such as poor bioavailability and side effects associated with conventional drug delivery methods. Among these strategies, the use of prodrugs offers a viable approach by leveraging enzymatic or controlled chemical transformations in vivo to enhance drug efficacy and specificity. The advent of bioorthogonal chemistry has revolutionized prodrug activation, providing a multitude of activation strategies beyond conventional methods. This review explores the integration of bioorthogonal chemistry, particularly transition metal catalysis, into prodrug activation strategies, with a focus on the use of macromolecular scaffolds as platforms to enable and localize these chemistries in biological environments. Specifically, this review focuses on the growing field of in situ bond-forming synthesis mediated by transition metal catalysts, often enabled by the use of macromolecular platforms. By forming carbon-carbon or carbon-heteroatom bonds intra- or intermolecularly, this approach offers advantages over traditional uncaging strategies through the absence of the pharmacoactive motif in the prodrug. We emphasize the central role of macromolecular platforms in integrating bioorthogonal chemistries into multimodal systems that enable targeting strategies and stimuli-responsive behavior, both crucial for achieving site-specific activation and minimizing off-target effects. We conclude that the future of this field lies with the development of retrosynthetic prodrug design, and the use and development of multimodular macromolecular platforms to host and enable new bioorthogonal transition metal catalysis.

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来源期刊
Journal of materials chemistry. B
Journal of materials chemistry. B 化学科学, 工程与材料, 生命科学, 分析化学, 高分子组装与超分子结构, 高分子科学, 免疫生物学, 免疫学, 生化分析及生物传感, 组织工程学, 生物力学与组织工程学, 资源循环科学, 冶金与矿业, 生物医用高分子材料, 有机高分子材料, 金属材料的制备科学与跨学科应用基础, 金属材料, 样品前处理方法与技术, 有机分子功能材料化学, 有机化学
CiteScore
12.00
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0.00%
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1 months
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