Chemoselective methionine bioconjugation with alkyne-bearing oxaziridine and alkyne-bearing iodonium salts was investigated as a new platform for site-selective radiolabeling of proteins and peptides with fluorine-18. Alkyne-bearing sulfimide conjugates, resulting from oxaziridine modification, underwent copper-assisted alkyne–azide cycloaddition (CuAAC) with an ¹⁸F-labeled PEGylated azide to afford ¹⁸F-labeled triazoles in excellent radiochemical yields. Diazoester sulfonium salt bioconjugates, formed from alkyne-bearing 2-diazoiodonium salts, gave low yields of ¹⁸F-labeled triazoles and were shown to be unstable to CuAAC conditions. Photolytic removal of the diazo group, however, afforded the trialkylsulfonium salt which smoothly underwent CuAAC with the ¹⁸F-labeled PEGylated azide to afford high radiochemical yields of the desired ¹⁸F-labeled click product. Overall, the results establish the viability of chemoselective methionine bioconjugation as a method for preparing site-selective ¹⁸F-labeled PET radioligands.

中文翻译：

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化学选择性蛋氨酸的生物缀合：蛋白质和多肽的位点选择性氟18标记。

带有炔烃的恶唑烷盐和带有炔烃的碘鎓盐的化学选择性蛋氨酸生物缀合被研究为氟18蛋白质和肽进行位点选择性放射性标记的新平台。由恶唑烷修饰得到的含炔磺酰亚胺共轭物，与¹⁸ F标记的聚乙二醇化叠氮化物进行铜助炔-叠氮化物环加成（CuAAC），以优异的放射化学产率得到¹⁸ F标记的三唑。由含炔的2-重氮碘鎓盐形成的重氮酯ester盐生物共轭物，收率低，含¹⁸ F标记的三唑，对CuAAC条件不稳定。然而，通过光解法去除重氮基团，可得到三烷基ulf盐，该盐可以顺利地与¹⁸ F标记的PEG化叠氮化物可提供所需¹⁸ F标记的点击产物的高放射化学产率。总的来说，该结果确立了化学选择性蛋氨酸生物缀合的可行性，作为制备位点选择性¹⁸ F标记PET放射性配体的方法。