10.1080/15257779408010676
The research aimed to develop potential affinity probes for adenylyl cyclase by synthesizing a series of 3'-substituted 2',5'-dideoxyadenosine analogs. The study focused on leveraging the enzyme's sensitivity to "P"-site-mediated inhibition and its tolerance for large 3'-ribose substitutions. The researchers encountered challenges with traditional synthesis methods due to poor coupling efficiencies and solubility issues with 2',5'-dideoxyadenosine. To address these, they developed an alternative approach involving the formation of symmetric aryl anhydrides, which were then coupled to 2',5'-dideoxyadenosine using base-catalyzed esterification. Key chemicals used in the research included 2',5'-dideoxyadenosine, various aryl acids (such as (4-nitrophenyl)-acetic acid and (4-azido-3-iodophenyl)-acetic acid), and coupling agents like DCC (dicyclohexylcarbodiimide) and DMAP (4-dimethylaminopyridine). The synthesized compounds were tested for their ability to inhibit adenylyl cyclase, with the nitro-analogs showing higher potency than the azido-iodo analogs. The study concluded that these analogs could serve as useful tools for studying the structure-function relationships of adenylyl cyclase, particularly in elucidating the characteristics of the "P"-site domain across different isozymes. Future work is suggested to further explore and identify additional covalent affinity ligands for adenylyl cyclase.