Chemistry Research Laboratory , University of Oxford , 12 Mansfield Road , Oxford OX1 3TA , U.K.
Radiobiology Research Institute, Department of Oncology , University of Oxford , Headington, Oxford OX3 7LJ , U.K.
J Am Chem Soc. 2020 Jan 22;142(3):1180-1185. doi: 10.1021/jacs.9b11709. Epub 2020 Jan 13.
F labeling strategies for unmodified peptides with [F]fluoride require F-labeled prosthetics for bioconjugation more often with cysteine thiols or lysine amines. Here we explore selective radical chemistry to target aromatic residues applying C-H F-trifluoromethylation. We report a one-step route to [F]CFSONH from [F]fluoride and its application to direct [F]CF incorporation at tryptophan or tyrosine residues using unmodified peptides as complex as recombinant human insulin. The fully automated radiosynthesis of octreotide[Trp(2-CFF)] enables in vivo positron emission tomography imaging.
对于未修饰的肽，F 标记策略通常需要使用 F 标记的假肢进行生物偶联，这些假肢通常与半胱氨酸硫醇或赖氨酸胺结合。在这里，我们探索了选择性自由基化学，以应用 C-H F-三氟甲基化来靶向芳香族残基。我们报告了一种从 F-氟化物一步合成[F]CFSONH 的方法，以及将其应用于使用未修饰的肽（如重组人胰岛素）直接在色氨酸或酪氨酸残基上进行[F]CF 掺入的方法。奥曲肽[Trp（2-CFF）]的全自动放射性合成可实现体内正电子发射断层扫描成像。
