SYNTHESIS AND IMMUNOSTIMULATING PROPERTIES OF LIPOPHILIC ESTER AND ETHER MURAMYL PEPTIDE DERIVATIVES

Macrophages can become cytotoxic toward tumor cells when activated by immunomodulators. Three different muramyl peptides were synthesized: o ne hydrolyzable Lipophilic ester derivative (MTP-Chol) and two nonhydr olyzable lipophilic ether derivatives (MTP-octadecane and MTP-heptadec afluorooctadecane). Activation of the RAW 264.7 cell line was studied by measuring nitrite production as an indication of NO-synthase activi ty. The lipophilic ester derivative, incorporated within nanocapsules, was as active as free muramyl dipeptide, whereas the lipophilic ether derivatives were unable to activate macrophages. MTP-octadecane in mi cellar form was not capable of inducing macrophage cytotoxicity either . These results indicate that lipophilic muramyl peptides need to be h ydrolyzed to yield a hydrosoluble metabolite in order to activate macr ophages.