Late-Stage Functionalisation of Cyclic Guanosine Monophosphate - Adenosine Monophosphate

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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.