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2‐(Glucosylthio)ethyl Groups as Potential Biolabile Phosphate‐ Protecting Groups of Mononucleotides
Author(s) -
Schlienger Nathalie,
Périgaud Christian,
Aubertin AnneMarie,
Thumann Christine,
Gosselin Gilles,
Imbach JeanLouis
Publication year - 1999
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/(sici)1522-2675(19991110)82:11<2044::aid-hlca2044>3.0.co;2-y
Subject(s) - chemistry , prodrug , phosphate , nucleoside , protecting group , enzyme , combinatorial chemistry , in vitro , human immunodeficiency virus (hiv) , substrate (aquarium) , nucleoside analogue , stereochemistry , drug , biochemistry , organic chemistry , pharmacology , medicine , alkyl , oceanography , family medicine , geology
The in vitro anti‐HIV effects and the stability studies of mononucleoside phosphotriester derivatives 1 – 3 of 3′‐azido‐3′‐deoxythymidine (AZT) containing 2‐(glucosylthio)ethyl moieties as potential biolabile phosphate‐protecting groups are reported. The results of the anti‐HIV evaluation demonstrate that the described compounds act via the release of the free nucleoside analogue and cannot be considered as mononucleotide prodrugs (pronucleotides). These data can be related to the lack of substrate affinity of these derivatives towards target‐enzymes as corroborated by decomposition studies in various media and experiments with a purified β ‐ D glucosidase.