ANTISENSE OLIGODEOXYNUCLEOSIDE PHOSPHOROTHIOATES NONSPECIFICALLY INHIBIT INVASION OF RED-BLOOD-CELLS BY MALARIA PARASITES

Anti-sense and sense oligodeoxynucleoside phosphorothioates, based on analysis of the secondary structure of Plasmodium falciparumdihydrofol ate reductase-thymidylate synthase mRNA, were synthesized. Their effec ts on P. falciparum growth in vitro were examined by microscopy and [H -3] hypoxanthine incorporation. Both anti-sense and sense oligodeoxynu cleoside phosphorothioares inhibit invasion of red blood cells by mero zoites and this is interpreted as being caused by their polyanionic na ture. Specific anti-sense effects of the oligonucleoside phosphorothio ates could not however be demonstrated. (C) 1996 Academic Press, Inc.