Chemoselective Methionine Bioconjugation: Site-Selective Fluorine-18 Labeling of Proteins and Peptides
Daniel Lin, Michael A. Wallace, Alban J. Allentoff, David J. Donnelly, Erin Gomes, Kim Voronin, Sharon Gong, Richard Y.‐C. Huang, Ho Kim, Janet Caceres‐Cortes, Samuel J. Bonacorsi
Abstract
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.