Adjuvant activities of quinonyl-N-acetyl muramyl dipeptides in mice and guinea pigs.
The adjuvant and tumor-suppressive activities of the quinonyl [2,3-dimethoxy-5-methyl-6-(9'-carboxynonyl)-1,4-benzoquinone (QS-10)] derivatives of N-acetyl muramyl dipeptides were examined. N-Acetyl muramyl-L-valyl-D-isoglutamine (MurNac-L-Val-D-isoGln), QS-10-MurNAc-L-Val-D-isoGln, and their methyl esters were shown to have potent adjuvant activity on the induction of delayed-type hypersensitivity to monoazobenzenarsonate-N-acetyl-L-tyrosine in guinea pigs and on the primary immune response against sheep erythrocytes in vitro; however, only QS-10-MurNAc-L-Val-D-isoGln methyl ester, i.e., QS-10-MurNAc-L-Val-D-Glu(OCH3)NH2 (quinonyl-MDP-66), was shown to be an active adjuvant for the induction of allogeneic killer T cells in mice and the suppression of tumor growth in syngeneic mice when it was administered as a suspension in phosphate-buffered saline. The effectiveness of the chain length of the quinonyl moiety in quinonyl-MDP-66 and the replacement of the L-valine residue with L-serine or L-threonine were also examined in comparison with the adjuvant and tumor-suppressive activities of quinonyl-MDP-66.
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000276:Adjuvants, Immunologic; D000818:Animals; D000917:Antibody Formation; D000970:Antineoplastic Agents; D003602:Cytotoxicity, Immunologic; D005260:Female; D006020:Glycopeptides / Q000494:pharmacology*; D006168:Guinea Pigs; D006968:Hypersensitivity, Delayed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D006020:Glycopeptides; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C023846:quinonyl-MDP-66