title: Synthesis and enzymatic deprotection of fully protected 2'-5' oligoadenylates (2-5A): towards a prodrug strategy for short 2-5A.
abstract: 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.
authors.affiliation: Department of Chemistry, University of Turku, Turku. emilia.kiuru@utu.fi
authors.forename: Emilia
authors.initials: E
authors.lastname: Kiuru
authors.forename: Mikko
authors.initials: M
authors.lastname: Ora
authors.forename: Leonid
authors.initials: L
authors.lastname: Beigelman
authors.forename: Lawrence
authors.initials: L
authors.lastname: Blatt
authors.forename: Harri
authors.initials: H
authors.lastname: Lönnberg
mesh_terms: D000227:Adenine Nucleotides / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D043182:Carboxylesterase / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D009843:Oligoribonucleotides / Q000737:chemistry* / Q000378:metabolism; D011355:Prodrugs / Q000737:chemistry* / Q000378:metabolism; D013552:Swine
chemical_list: D000227:Adenine Nucleotides; D009843:Oligoribonucleotides; D011355:Prodrugs; C023505:2',5'-oligoadenylate; D043182:Carboxylesterase