Nucleoside analogues previously found to be inactive against HIV may be activated by simple chemical phosphorylation.

Abstract:

:Nucleoside analogues previously found to be inactive against the human immunodeficiency virus (HIV) may be activated by simple chemical derivatisation. As part of our effort to deliver masked phosphates inside living cells we have discovered that certain phosphate triester derivatives of inactive nucleoside analogues become inhibitors of HIV replication. This discovery underlies the importance of the masked phosphate approach, and has significant implications for the future design of chemotherapeutic nucleoside analogues. If highly modified nucleoside analogues may be active without the intervention of nucleoside kinase enzymes, major advantage may accrue in terms of low toxicity and enhanced selectivity. Moreover, the increased structural freedom may have implications for dealing with the emergence of resistance. The concept herein described as 'kinase bypass' may thus stimulate the discovery of a new generation of antiviral agents.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

McGuigan C,Kinchington D,Wang MF,Nicholls SR,Nickson C,Galpin S,Jeffries DJ,O'Connor TJ

doi

10.1016/0014-5793(93)81580-s

subject

Has Abstract

pub_date

1993-05-17 00:00:00

pages

249-52

issue

3

eissn

0014-5793

issn

1873-3468

pii

0014-5793(93)81580-S

journal_volume

322

pub_type

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