Drake Christopher R, Sevillano Natalia, Truillet Charles, Craik Charles S, VanBrocklin Henry F, Evans Michael J
Department of Radiology and Biomedical Imaging, University of California San Francisco , Suite 350, 185 Berry Street, San Francisco, California 94107, United States.
Department of Pharmaceutical Chemistry, University of California San Francisco , Genentech Hall, S-514, 600 16th Street, San Francisco, California 94158, United States.
ACS Chem Biol. 2016 Jun 17;11(6):1587-94. doi: 10.1021/acschembio.6b00172. Epub 2016 Mar 31.
New methodologies for site-specifically radiolabeling proteins with (18)F are required to generate high quality radiotracers for preclinical and clinical applications with positron emission tomography. Herein, we report an approach by which we use lipoic acid ligase (LplA) to conjugate [(18)F]-fluorooctanoic acid to an antibody fragment bearing the peptide substrate of LplA. The mild conditions of the reaction preserve antibody immunoreactivity, and the efficiency of LplA allows for >90% yield even with very small amounts of peptidic precursor (1-10 nmol). These features are advantageous compared to the current gold standard in the field. Moreover, the methodology introduces a new application for an important tool in chemical biology.
需要新的方法来用（18）F对蛋白质进行位点特异性放射性标记，以生成用于正电子发射断层扫描的临床前和临床应用的高质量放射性示踪剂。在此，我们报告了一种方法，即我们使用硫辛酸连接酶（LplA）将[（18）F] - 氟辛酸与带有LplA肽底物的抗体片段偶联。反应的温和条件保留了抗体的免疫反应性，并且即使使用非常少量的肽前体（1 - 10 nmol），LplA的效率也能实现> 90％的产率。与该领域当前的金标准相比，这些特征具有优势。此外，该方法为化学生物学中的一种重要工具引入了新的应用。
