Late-Stage Functionalisation of Cyclic Guanosine Monophosphate - Adenosine Monophosphate

该项目旨在探索cGAMP的后期功能化，以改善分子的STING结合和/或药代动力学特性。为此，首先将采用Gaunt及其同事开发的鸟嘌呤胺化反应对cGAMP进行修饰。该反应将使用cGAMP代理底物进行优化，以允许纳米摩尔尺度的cGAMP操作。将在反应中测试一系列胺，并在生物分析中从化合物中收集结合数据。还将建立cGAMP的大规模生产方法，以减轻大量购买该化合物的财政负担。继C8胺化反应之后，其他后期功能化策略将被追求，目标是产生新的cGAMP类似物。

This project aims to explore the late-stage functionalisation of cGAMP in order to improve STING binding and/or pharmacokinetic properities of the molecule. To that end, firstly a guanine amination reaction developed by Gaunt and coworkers will be employed for cGAMP modification. This reaction will be optimised using a cGAMP proxy substrate to allow for nanomolar scale manipulations of cGAMP. A scope of amines will be tested in the reaction, with binding data being collected from the compounds in biological assays. A large-scale production method for cGAMP will also be established to mitigate the financial burden of purchasing large quantities of the compound. Following on from the C8 amination reaction, other late-stage functionalisation strategies will be pursued with the goal of generating novel cGAMP analogues.