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: one hydrolyzable lipophilic ester derivative (MTP-Chol) and two nonhydrolyzable lipophilic ether derivatives (MTP-octadecane and MTP-heptadecafluorooctadecane). Activation of the RAW 264.7 cell line was studied by measuring nitrite production as an indication of NO-synthase activity. 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 micellar form was not capable of inducing macrophage cytotoxicity either. These results indicate that lipophilic muramyl peptides need to be hydrolyzed to yield a hydrosoluble metabolite in order to activate macrophages.
Merhi
G
G
Laboratoire de Pharmacotechnie-Biopharmacie, URA CNRS 1218, Université de Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry, France.
Coleman
A W
AW
Devissaguet
J P
JP
Barratt
G M
GM
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000276:immunology; D000818:Animals; D004790:Enzyme Induction; D008262:Macrophage Activation / Q000187:drug effects; D051379:Mice; D019001:Nitric Oxide Synthase / Q000096:biosynthesis
D000119:Acetylmuramyl-Alanyl-Isoglutamine; D019001:Nitric Oxide Synthase