Chemoselective Methionine Bioconjugation: Site-Selective Fluorine-18 Labeling of Proteins and Peptides

• Published in: Bioconjugate chemistry Vol. 31; no. 8; pp. 1908 - 1916
• Main Authors: Lin, Daniel, Wallace, Michael, Allentoff, Alban J, Donnelly, David J, Gomes, Erin, Voronin, Kim, Gong, Sharon, Huang, Richard Y.-C, Kim, Ho, Caceres-Cortes, Janet, Bonacorsi, Samuel
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 19.08.2020; Amer Chemical Soc
• Subjects: Alkynes; Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry; Chemistry, Multidisciplinary; Chemistry, Organic; Cycloaddition; Fluorine; Fluorine isotopes; Life Sciences & Biomedicine; Methionine; Peptides; Physical Sciences; Proteins; Radiochemistry; Radioisotopes; Radiolabelling; Salts; Science & Technology; Sulfonium salts; Triazoles; CONJUGATION; DESIGN; GENERATION; RADIOSYNTHESIS
• ISSN: 1043-1802; 1520-4812
• DOI: 10.1021/acs.bioconjchem.0c00256

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.