A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Synthesis and Enzymatic Deprotection of Fully Protected 2 '-5 ' Oligoadenylates (2-5A): Towards a Prodrug Strategy for Short 2-5A
Tekijät: Kiuru E, Ora M, Beigelman L, Blatt L, Lonnberg H
Kustantaja: WILEY-V C H VERLAG GMBH
Julkaisuvuosi: 2012
Lehti: Chemistry and Biodiversity
Tietokannassa oleva lehden nimi: CHEMISTRY & BIODIVERSITY
Lehden akronyymi: CHEM BIODIVERS
Numero sarjassa: 4
Vuosikerta: 9
Numero: 4
Aloitussivu: 669
Lopetussivu: 688
Sivujen määrä: 20
ISSN: 1612-1872
DOI: https://doi.org/10.1002/cbdv.201100144
Rinnakkaistallenteen osoite: 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.
Avainsanat:
Hog liver carboxyesterase, Oligoadenylate, Oligonucleotides, Prodrugs, Protecting groups
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