Synthesis and enzymatic deprotection of fully protected 2′-5′ oligoadenylates (2-5A): Towards a prodrug strategy for short 2-5A

Article abstract of DOI:10.1002/cbdv.201100144

Fully protected pA2′p5′A2′p5′A trimers 1a and 1b have been prepared as prodrug candidates for a short 2′-5′ oligoadenylate, 2-5A, and its 3′-O-Me analog, respectively. The kinetics of hog liver carboxyesterase (HLE)-triggered deprotection in HEPES buffer (pH 7.5) at 37° has been studied. The deprotection of 1a turned out to be very slow, and 2-5A never appeared in a fully deprotected form. By contrast, a considerable proportion of 1b was converted to the desired 2-5A trimer, although partial removal of the 3′-O-[(acetyloxy)methyl] group prior to exposure of the adjacent phosphodiester linkage resulted in 2′, 5′→3′,5′ phosphate migration and release of adenosine as side reactions.