Adjuvant activities of quinonyl-N-acetyl muramyl dipeptides in mice and guinea pigs

Abstract

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.