Advances in the Application of Click Chemistry/Bioorthogonal Reactions in Drug Development

点击化学(Click Chemistry)是由诺贝尔化学奖得主K. Barry Sharpless提出的一种高效模块化合成策略，其特点是通过高选择性、高产率的化学反应快速构建复杂分子。生物正交反应(Bioorthogonal Chemistry)则由诺贝尔化学奖得主Carolyn R. Bertozzi开创，特指在生物体系中进行的、不干扰正常生理过程的化学反应，具有生物相容性好、选择性高等特点。这两种化学策略在药物开发中展现出独特优势：点击化学提供了快速、灵活的分子构建方法，而生物正交反应则实现了在复杂生物环境下的精准化学转化。本文将系统综述这两类反应的最新发展，重点阐述其在药物分子设计、生物标记、药物递送等领域的创新应用，并深入探讨当前面临的挑战及未来发展方向。Click Chemistry, proposed by Nobel Chemistry Prize laureate K. Barry Sharpless, is an efficient modular synthesis strategy characterized by rapid construction of complex molecules through highly selective, high-yield chemical reactions. Bioorthogonal Chemistry, pioneered by Nobel Chemistry Prize laureate Carolyn R. Bertozzi, specifically refers to chemical reactions that occur in biological systems without interfering with normal physiological processes, featuring good biocompatibility and high selectivity. These two chemical strategies show unique advantages in drug development: Click Chemistry provides quick and flexible methods for molecular construction, while Bioorthogonal reactions enable precise chemical transformations in complex biological environments. This article systematically reviews the latest developments of these two types of reactions, focusing on their innovative applications in drug molecule design, biological labeling, and drug delivery, while also exploring current challenges and future development directions.