Nucleic Acids Research, 1989, Vol. 17, No. 24 10171-10177
© 1989
Articles |
Synthesis and evaluation of some novel phosphate and phosphinate derivatives of araA. Studies on the mechanism of action of phosphate triesters
Department of Chemistry, University College London 20 Gordon Street, London WC1H 0AJ 1Department of Chemical Pathology, University College and Middlesex School of Medicine Windeyer Building, Cleveland Street London W1P 6DB, UK
*To Whom Correspondance should be addressed
Received October 23, 1989. Revised November 20, 1989. Accepted November 20, 1989.
A number of novel phosphinate and phosphate triester derivatives of the anti-viral nucleoside analogue araA have been prepared. Spectroscopic and analytical data have been collected on both the reagents and the nucleotides. An in vitro assay indicated inhibition of DNA synthesis by mammalian cells, by each of the nucleotide derivatives, in the range 3—30µM. Inhibition was reduced, but not abolished, for the phosphinates relative to the phosphates. These results are consistent with a mode of action involving release of the free nucleoside araA and the nucleotide araAMP.