逆电子需求的狄尔斯-阿尔德反应在生物正交化学领域的发展与应用

Development and applications of inverse-electron-demand Diels-Alder reaction in bioorthogonal chemistry

逆电子需求的狄尔斯-阿尔德(IEDDA)反应由于其生物兼容性好、反应专一性高、反应速率快等优点逐渐成为最受关注的生物正交化学反应.因此,研究者围绕IEDDA反应,从包括反应机理、底物合成、效率优化以及反应应用等多个角度进行了深入研究与探索,开发了分别用于生物正交偶联和生物正交断键的IEDDA反应.本文首先从反应的发展和优化角度对IEDDA反应进行了介绍,随后归纳总结了IEDDA分别作为偶联反应和断键反应在生物大分子标记、药物运输、药物动力学研究、蛋白质调控与功能激活、前药释放、siRNA激活以及RNA固相纯化等领域的生物应用.最后,对IEDDA反应的进一步研究与应用进行了展望,期待通过对更优反应对的开发以及更广泛生物应用的探索,将生物正交化学的发展与应用推进到一个新的高度.

Inverse-electron-demand Diels-Alder(IEDDA) reaction has become the most attractive bioorthogonal reaction due to its advantages of good biocompatibility, high reaction specificity and fast reaction kinetics. Therefore,extensive studies have been conducted in terms of reaction mechanism, reactants synthesis, chemistry optimization,biological applications, etc., for IEDDA ligation and cleavage reactions respectively. In this review, first of all, we introduce the development and optimizations of the IEDDA reaction, followed by its biological applications including biomolecules labeling, protein manipulation, activation, drug delivery, pharmacokinetics study, prodrug releasing,siRNA activation and solid phase RNA purification. At last, we envision that further studies and applications of the IEDDA reaction are in demand, and expect that by exploring more optimized reaction pairs and wider biological applications, the research area of bioorthogonal chemistry would rush into a new era.