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

FEBS Letters

Wang, Meng Fang¹  McGuigan, Christopher¹  O'Connor, Timothy J.²  Galpin, Sarah²  Nicholls, Simon R.³  Nickson, Caleb³  Kinchington, Derek²  Jeffries, Donald J.² 

[1] Department of Chemistry, University of Southampton, Highfield, Southampton, S09 5NH, UK;Department of Virology, St. Bartholomew's Hospital Medical College, West Smithfield, London, ECIA 7BE, UK;Department of Chemistry, University College London, 20, Gordon Street, London, WC1H OAJ, UK

关键词: Nucleoside;    Nucleotide;    Anti-HIV;   

DOI  :  10.1016/0014-5793(93)81580-S

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown