A One-Pot Three-Component Radiochemical Reaction for Rapid Assembly of 125I-Labeled Molecular Probes

详细信息    查看全文

• 作者：Ran Yan ; Kerstin Sander ; Eva Galante ; Vineeth Rajkumar ; Adam Badar ; Mathew Robson ; Ethaar El-Emir ; Mark F. Lythgoe ; R. Barbara Pedley ; Erik 脜rstad
• 刊名：The Journal of the American Chemical Society
• 出版年：2013
• 出版时间：January 16, 2013
• 年：2013
• 卷：135
• 期：2
• 页码：703-709
• 全文大小：378K
• 年卷期：v.135,no.2(January 16, 2013)
• ISSN：1520-5126

文摘

Nuclear imaging in conjunction with radioactive tracers enables noninvasive measurements of biochemical events in vivo. However, access to tracers remains limited due to the lack of methods for rapid assembly of radiolabeled molecules with the prerequisite biological activity. Herein, we report a one-pot, three-component, copper(II)-mediated reaction of azides, alkynes, and [¹²⁵I]iodide to yield 5-[¹²⁵I]iodo-1,2,3-triazoles. Using a selection of azides and alkynes in a combinatorial approach, we have synthesized a library of structurally diverse ¹²⁵I-labeled triazoles functionalized with bioconjugation groups, fluorescent dyes, and biomolecules. Our preliminary biological evaluation suggests that 5-[¹²⁵I]iodo-1,2,3-triazoles are resistant to deiodination in vivo, both as small molecular probes and as antibody conjugates. The ability to incorporate radioactive iodide into triazoles directly from the parent azides and alkynes makes the method broadly applicable and offers the potential to rapidly assemble molecular probes from an array of structurally diverse, and readily available, building blocks.