Fluorinase C-18F bond catalysis

同位素氟-18被广泛用作正电子发射断层扫描（PET）的放射性核苷酸。同位素是由[18O]-水在回旋加速器上产生的，通常在医院环境中。然后用离子交换色谱法干燥氟化物，通常用于亲核化学。不同寻常的是，该项目将使用一种在水中直接起作用的酶来产生18F-C键。这样做的优点是不需要离子交换或氟离子干燥，底物可以是水溶性肽。该项目将探索癌症相关肽的放射标记，用于临床成像，使用氟酶在C-F键形成催化剂上。该方法已开发，以实现“最后一步”标记在水缓冲液中，是完全兼容的，以保持标记化学过程中的肽的完整性。目前，该项目的目标是探索这种氟酶催化的转绿原化的范围，并将其多功能性扩展到[18F]-肽，并扩展到更高分子量和更高结构复杂性的生物聚合物。学生将接受现代化学生物学技术的广泛培训（有机合成，蛋白质表达和纯化，生物偶联策略和生物转化）。学生将了解合成和生物化学网络实验室的安全规程。学生还应获得放射化学正电子发射断层扫描的基本训练。

The isotope fluorine-18 is used widely as a radionucleotide for positron emission tomography (PET). The isotope is generated from [18O]-water on a cyclotron, usually in hospital environments. The fluoride is then dried by ion-exchange chromatography and generally used in nucleophilic chemistry. Unusually the project will use an enzyme that works in water directly to generate the 18F-C bond. The advantage of this is that there is no ion-exchange or drying of the fluoride ion required, and that substrates can be water soluble peptides. The project will explore the radiolabelling of cancer relevant peptides for clinical imaging, using the fluorinase enzyme at the C-F bond forming catalyst.The method has been developed to achieve 'last step' labelling in aqueous buffer and is entirely compatible to maintaining the integrity of peptides during labelling chemistry. The aim of the project now is to explore the scope and extend the versatility of this fluorinase catalyzed transhalogenation to [18F]-peptides, and extend to higher mol. weight and higher structural complexity biopolymers. The student will receive an extensive training in the techniques for modern chemical biology (organic synthesis, protein expression and purification, bioconjugation strategies and biotransformations).The student weill become aware of synthesis and biochemistry web lab safety protocolsThe student should also gain a basic training in radiochemistry for positron emission tomography.