SYNTHESIS AND BIOLOGICAL EVALUATION OF A NEW N4-(N-FORMYL PEPTIDE)-2',3'-DIDEOXY-3'-THIACYTIDINE AS ANTI-HIV PRODRUG

The synthesis of a new analogue of 2,3'-dideoxy-3'-thiacytidine 9 cova lently linked to an N-formyl methionyl leucyl phenylalanine peptide is described. This new prodrug analogue has been tested on the one hand as activator of human polymorphonuclear leukocytes (an EC50 value of 1 .8 10(-5) M was determined from dose-response curve for superoxide pro duction) and on the other hand as inhibitor Of the syncitium formation caused by HIV-1 in MT4-cells (IC50 = 8.0 +/- 0.8 muM). In so far as t his new prodrug possesses these two biological properties, it represen ts a useful ''chemical-head' capable of targeting specific receptors l ocated on leukocytes membranes.