Synthesis and Enzymatic Deprotection of Fully Protected 2 '-5 ' Oligoadenylates (2-5A): Towards a Prodrug Strategy for Short 2-5A



: Kiuru E, Ora M, Beigelman L, Blatt L, Lonnberg H

Publisher: WILEY-V C H VERLAG GMBH

: 2012

: Chemistry and Biodiversity

: CHEMISTRY & BIODIVERSITY

: CHEM BIODIVERS

: 4

: 9

: 4

: 669

: 688

: 20

: 1612-1872

DOI: https://doi.org/10.1002/cbdv.201100144

: https://research.utu.fi/converis/portal/detail/Publication/1463654


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 degrees 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.

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