A1 Refereed original research article in a scientific journal

Synthesis and Enzymatic Deprotection of Biodegradably Protected Dinucleoside-2 ',5 '-monophosphates: 3-(Acetyloxy)-2,2-bis(ethoxycarbonyl)propyl Phosphoesters of 3 '-O-(Acyloxymethyl)adenylyl-2 ',5 '-adenosines




AuthorsKiuru E, Ora M, Beigelman L, Blatt L, Lonnberg H

PublisherWILEY-BLACKWELL

Publication year2011

JournalChemistry and Biodiversity

Journal name in sourceCHEMISTRY & BIODIVERSITY

Journal acronymCHEM BIODIVERS

Number in series2

Volume8

Issue2

First page 266

Last page286

Number of pages21

ISSN1612-1872

DOIhttps://doi.org/10.1002/cbdv.201000288(external)


Abstract
As a first step towards a viable prodrug strategy for short oligoribonucleotides, such as 2-5A and its congeners, adenylyl-2',5'-adenosines bearing a 3-(acetyloxy)-2,2-bis(ethoxycarbonyl)propyl group at the phosphate moiety, and an (acetyloxy)methyl-or a (pivaloyloxy)methyl-protected 3'-OH group of the 2'-linked nucleoside have been prepared. The enzyme-triggered removal of these protecting groups by hog liver carboxyesterase at pH 7.5 and 37 degrees has been studied. The (acetyloxy)methyl group turned out to be too labile for the 3'-O-protection, being removed faster than the phosphate-protecting group, which results in 2',5'- to 3',5'-isomerization of the internucleosidic phosphoester linkage. In addition, the starting material was unexpectedly converted to the 5'-O-acetylated derivative. (Pivaloyloxy)methyl group appears more appropriate for the purpose. The fully deprotected 2',5'-ApA was accumulated as a main product, although, even in this case, the isomerization of the starting material takes place.


Research Areas



Last updated on 2024-26-11 at 21:27