Fluorinase C-18F bond catalysis

氟酶 C-18F 键催化

• 批准号: 1794883
• 金额: --
• 依托单位: University of St Andrews
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1794883
• 关键词: Fluorinase; 18F; bond; catalysis

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.

同位素氟-18被广泛用作正电子发射断层扫描（PET）的放射性核素。这种同位素是在回旋加速器上由[18 O]-水产生的，通常在医院环境中。然后通过离子交换色谱干燥氟化物，通常用于亲核化学。不同寻常的是，该项目将使用一种直接在水中作用的酶来产生18 F-C键。这样做的优点是不需要氟离子的离子交换或干燥，并且底物可以是水溶性肽。该项目将探索用于临床成像的癌症相关肽的放射性标记，使用氟酶在C-F键形成催化剂。该方法已被开发用于在水性缓冲液中实现“最后一步”标记，并且在标记化学过程中完全兼容以保持肽的完整性。该项目现在的目的是探索范围，并将这种氟化酶催化的转卤化的多功能性扩展到[18F]-肽，并扩展到更高的摩尔比。重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（有机合成，蛋白质表达和纯化，生物共轭策略和生物转化）的广泛培训。学生将了解合成和生物化学网络实验室的安全协议。学生还应获得正电子发射断层扫描放射化学的基本培训。