Apyrogenic synthetic desmuramyldipeptide, LK-409, with immunomodulatory properties.
The synthesis and some immunological characteristics of a new desmuramyl dipeptide 7-oxooctanoyl-L-alanyl-D-isoglutamine (LK-409) are presented. The effects of this compound were compared with those of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP). The influence of LK-409 on the number of B and T cells in spleen and the number of peritoneal macrophages was studied; Jerne's plaque forming cells assay was performed to monitor the effect of B cell differentiation. The blast transformation of T cells stimulated with concanavalin A was used to detect the influences on T lymphocytes. The activation of macrophages was studied as well. In contrast to MDP, LK-409 was apyrogenic in the doses applied but had similar immunomodulatory properties. Tested immunological properties and the absence of pyrogenicity and low toxicity make LK-409 a candidate for an immunomodulatory drug and a model molecule suitable for studying and understanding the dual activity of the MDP and its analogues.
Sollner
M
M
Department of Pharmacy, Faculty of Natural Sciences and Technology, University of Ljubljana, Slovenia.
Kotnik
V
V
Pecar
S
S
Stace
A
A
Simcic
S
S
Povsic
L
L
Herzog-Wraber
B
B
Klampfer
L
L
Ihan
A
A
Grosman
P
P
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000276:immunology / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002452:Cell Count / Q000187:drug effects; D004151:Dipeptides / Q000138:chemical synthesis / Q000276:immunology / Q000494:pharmacology*; D005260:Female; D006462:Hemolytic Plaque Technique; D008213:Lymphocyte Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D011749:Pyrogens; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D000276:Adjuvants, Immunologic; D004151:Dipeptides; C079179:LK 409; D011749:Pyrogens; D013481:Superoxides; D000119:Acetylmuramyl-Alanyl-Isoglutamine