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 Lettjournal_title
FEBS lettersauthors
McGuigan C,Kinchington D,Wang MF,Nicholls SR,Nickson C,Galpin S,Jeffries DJ,O'Connor TJdoi
10.1016/0014-5793(93)81580-ssubject
Has Abstractpub_date
1993-05-17 00:00:00pages
249-52issue
3eissn
0014-5793issn
1873-3468pii
0014-5793(93)81580-Sjournal_volume
322pub_type
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