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New insights regarding the potential of the pronucleotide approach in antiviral chemotherapy. 1996
G Gosselin, and
J L Girardet, and
C Périgaud, and
S Benzaria, and
I Lefebvre, and
N Schlienger, and
A Pompon, and
J L Imbach
Laboratoire de Chimie Bioorganique, URA CNRS 488, Université de Montpellier II, France.
The rationale for a pronucleotide approach based on the use of phosphotriesters which incorporate enzyme-mediated bio-labile protection is discussed in detail. Among the studied bio-labile phosphate protecting groups, the S-acyl-2-thioethyl (SATE) groups appeared the most promising as exemplified in cell culture systems in the case of the pronucleotides of 3'-azido-3'-deoxythymidine, 2',3'-didehydro-3'-deoxythymidine, 2',3'-dideoxyadenosine and acyclovir In vivo implementations of such bis(SATE) pronucleotides have been planned for future animal studies.
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