Synthesis, mass spectral characterization and immunoadjuvant activity of some novel lipophilic derivatives of muramyl dipeptides.
Some novel lipophilic derivatives of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) have been prepared and rigorously evaluated by spectroscopic means. Fast atom bombardment and field desorption mass spectrometry provided information about both molecular weight and structural detail. The new MDP derivatives have been tested in guinea pigs for immunoadjuvant activity using egg albumin as the model antigen. Amongst these derivatives, 6-O-[3-(5-cholesten-3 beta-yloxycarbonyl) propionyl]-N-acetylmuramyl-L-alanyl-D-isoglutamine (CSMDP), 6-O-[3-1,2-dipalmitoyl-sn-glycero-3-carbonyl) propionyl]-N-acetylmuramyl-L-alanyl-D-isoglutamine (GSMDP) and N-palmitoyl muramyl-L-alanyl-D-isoglutamine (PMDP) possessed significantly better activity than MDP, as judged by the antigen-specific antibody and delayed hypersensitivity responses in the immunized animals. In addition, CSMDP was found to induce strong delayed hypersensitivity response even in saline. These three active compounds were also tested for their pyrogenic response in rabbits, and were found to be lesser pyrogenic than MDP. Some of these MDP derivatives hold promise as adjuvants in immunization.
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000633:toxicity; D000276:Adjuvants, Immunologic; D000818:Animals; D005260:Female; D006168:Guinea Pigs; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D011749:Pyrogens; D011817:Rabbits; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
D000276:Adjuvants, Immunologic; D007202:Indicators and Reagents; D011749:Pyrogens; D000119:Acetylmuramyl-Alanyl-Isoglutamine