Synthesis and modulation of cytokine production by two new adamantane substituted acyclic desmuramyldipeptide analogs.
Two new adamantyl-desmuramyldipeptides LK 415 and LK 517 with 1-adamantylcarboxamido moiety as a replacement for muramyldipeptide's N-acetylglucosamine fragment were synthesized. Their efficacy to modulate the production of cytokines was measured in vitro in ionomycin and phorbol-12-myristate-13-acetate (PMA) activated cultures of human peripheral blood mononuclear cells (PBMC), co-incubated with the substances tested. The results were compared with the activity of muramyldipeptide (MDP). All three substances are strong up-regulators of IL-12 synthesis and hence of the IFN gamma synthesis as well. While MDP and LK 415 are relatively ineffective in modulation of IL-2, IL-4 and IL-10 production in vitro, the synthesis of all three cytokines is considerably up-regulated when peripheral blood mononuclear cells are co-incubated with LK 517. It seems likely that the introduction of the diethyl phosphonate moiety into LK 517 is of great importance for the augmented T-cell cytokine production.
Gobec
S
S
Faculty of Pharmacy, Medical Faculty, University of Ljubljana, Slovenia.
Urleb
U
U
Simcic
S
S
Wraber
B
B
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000218:Adamantane / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D000276:Adjuvants, Immunologic / Q000138:chemical synthesis* / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004151:Dipeptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000276:Adjuvants, Immunologic; D016207:Cytokines; D004151:Dipeptides; D007378:Interleukins; C433772:LK 415; C433773:LK 517; D014409:Tumor Necrosis Factor-alpha; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D007371:Interferon-gamma; D000218:Adamantane