Department of Nuclear Engineering, Pakistan Institute of Engineering and Applied Sciences, Islamabad 45650, Pakistan.
IT Convergence Materials Group, Korea Institute of Industrial Technology, Cheonan 31056, Korea.
Molecules. 2019 Oct 2;24(19):3567. doi: 10.3390/molecules24193567.
In recent years, several catalyst-free site-specific reactions have been investigated for the efficient conjugation of biomolecules, nanomaterials, and living cells. Representative functional group pairs for these reactions include the following: (1) azide and cyclooctyne for strain-promoted cycloaddition reaction, (2) tetrazine and trans-alkene for inverse-electron-demand-Diels-Alder reaction, and (3) electrophilic heterocycles and cysteine for rapid condensation/addition reaction. Due to their excellent specificities and high reaction rates, these conjugation methods have been utilized for the labeling of radioisotopes (e.g., radiohalogens, radiometals) to various target molecules. The radiolabeled products prepared by these methods have been applied to preclinical research, such as in vivo molecular imaging, pharmacokinetic studies, and radiation therapy of cancer cells. In this review, we explain the basics of these chemical reactions and introduce their recent applications in the field of radiopharmacy and chemical biology. In addition, we discuss the significance, current challenges, and prospects of using bioorthogonal conjugation reactions.
近年来，人们研究了几种无催化剂的位点特异性反应，以实现生物分子、纳米材料和活细胞的高效偶联。这些反应的代表性官能团对包括以下几种：（1）叠氮化物和环辛炔用于应变促进环加成反应，（2）四嗪和反式烯烃用于逆向电子需求 Diels-Alder 反应，以及（3）亲电杂环和半胱氨酸用于快速缩合/加成反应。由于这些偶联方法具有优异的特异性和高反应速率，因此已将其用于将放射性同位素（例如放射性卤素、放射性金属）标记到各种靶分子上。通过这些方法制备的放射性标记产物已应用于临床前研究，例如体内分子成像、药代动力学研究和癌细胞的放射治疗。在本文中，我们解释了这些化学反应的基本原理，并介绍了它们在放射药物学和化学生物学领域的最新应用。此外，我们还讨论了使用生物正交偶联反应的意义、当前挑战和前景。
