Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Chemistry, Hunter College of the City University of New York, New York, NY, USA.
Nat Protoc. 2023 Jun;18(6):1659-1668. doi: 10.1038/s41596-023-00825-8. Epub 2023 Apr 26.
The 2022 Nobel Prize in Chemistry was awarded to Professors K. Barry Sharpless, Morten Meldal and Carolyn Bertozzi for their pioneering roles in the advent of click chemistry. Sharpless and Meldal worked to develop the canonical click reaction-the copper-catalyzed azide-alkyne cycloaddition-while Bertozzi opened new frontiers with the creation of the bioorthogonal strain-promoted azide-alkyne cycloaddition. These two reactions have revolutionized chemical and biological science by facilitating selective, high yielding, rapid and clean ligations and by providing unprecedented ways to manipulate living systems. Click chemistry has affected every aspect of chemistry and chemical biology, but few disciplines have been impacted as much as radiopharmaceutical chemistry. The importance of speed and selectivity in radiochemistry make it an almost tailor-made application of click chemistry. In this Perspective, we discuss the ways in which the copper-catalyzed azide-alkyne cycloaddition, the strain-promoted azide-alkyne cycloaddition and a handful of 'next-generation' click reactions have transformed radiopharmaceutical chemistry, both as tools for more efficient radiosyntheses and as linchpins of technologies that have the potential to improve nuclear medicine.
2022 年诺贝尔化学奖授予卡罗琳·贝托齐、摩顿·梅尔达尔和 K·巴里·夏普勒斯三位科学家，以表彰他们在点击化学发展方面的先驱作用。夏普勒斯和梅尔达尔致力于开发经典的点击反应——铜催化的叠氮-炔环加成反应，而贝托齐则通过创建生物正交应变促进的叠氮-炔环加成反应开辟了新的前沿领域。这两种反应通过促进选择性、高产率、快速和清洁的连接，以及提供操纵生命系统的前所未有的方法，彻底改变了化学和生物科学。点击化学已经影响了化学和化学生物学的各个方面，但很少有学科像放射性药物化学那样受到如此大的影响。速度和选择性在放射化学中的重要性使其成为点击化学的几乎量身定制的应用。在这篇观点文章中，我们讨论了铜催化的叠氮-炔环加成反应、应变促进的叠氮-炔环加成反应和少数“下一代”点击反应如何改变放射性药物化学，它们既是更高效的放射合成工具，也是具有改善核医学潜力的技术的关键。
