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. 1981 Jan;31(1):114–121. doi: 10.1128/iai.31.1.114-121.1981

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

I Saiki, Y Tanio, M Yamawaki, M Uemiya, S Kobayashi, T Fukuda, H Yukimasa, Y Yamamura, I Azuma
PMCID: PMC351759  PMID: 6971259

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.

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Selected References

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  1. Adam A., Ciorbaru R., Ellouz F., Petit J. F., Lederer E. Adjuvant activity of monomeric bacterial cell wall peptidoglycans. Biochem Biophys Res Commun. 1974 Feb 4;56(3):561–567. doi: 10.1016/0006-291x(74)90640-8. [DOI] [PubMed] [Google Scholar]
  2. Adam A., Devys M., Souvannavong V., Lefrancier P., Choay J., Lederer E. Correlation of structure and adjuvant activity of N-acetyl muramyl-L-alanyl-D-isoglutamine (MDP), its derivatives and analogues. Anti-adjuvant and competition properties of stereoisomers. Biochem Biophys Res Commun. 1976 Sep 7;72(1):339–346. doi: 10.1016/0006-291x(76)90999-2. [DOI] [PubMed] [Google Scholar]
  3. Azuma I., Kamisango K. I., Saiki I., Tanio Y., Kobayashi S., Yamamura Y. Adjuvant activity of N-acetyl muramyl dipeptides for the induction of delayed-type hypersensitivity to azobenzenearsonate-N-acetyl-L-tyrosine in guinea pigs. Infect Immun. 1980 Sep;29(3):1193–1196. doi: 10.1128/iai.29.3.1193-1196.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Azuma I., Sugimura K., Taniyama T., Yamawaki M., Yamamura Y. Adjuvant activity of mycobacterial fractions: adjuvant activity of synthetic N-acetylmuramyl-dipeptide and the related compounds. Infect Immun. 1976 Jul;14(1):18–27. doi: 10.1128/iai.14.1.18-27.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Azuma I., Sugimura K., Yamawaki M., Uemiya M., Kusumoto S., Okada S., Shiba T., Yamamura Y. Adjuvant activity of synthetic 6-O-"mycoloyl"-N-acetylmuramyl-L-alanyl-D-isoglutamine and related compounds. Infect Immun. 1978 Jun;20(3):600–607. doi: 10.1128/iai.20.3.600-607.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Azuma I., Taniyama T., Yamawaki M., Sugimura K., Yamamura Y. Adjuvant and antitumor activities of Nocardia cell-wall skeletons. Gan. 1976 Oct;67(5):733–736. [PubMed] [Google Scholar]
  7. Azuma I., Yamawaki M., Uemiya M., Saiki I., Tanio Y., Kobayashi S., Fukuda T., Imada I., Yamamura Y. Adjuvant and antitumor activities of quinonyl-N-acetylmuramyldipeptides. Gan. 1979 Dec;70(6):847–848. [PubMed] [Google Scholar]
  8. Brunner K. T., Mauel J., Rudolf H., Chapuis B. Studies of allograft immunity in mice. I. Induction, development and in vitro assay of cellular immunity. Immunology. 1970 Apr;18(4):501–515. [PMC free article] [PubMed] [Google Scholar]
  9. Damais C., Parant M., Chedid L., Lefrancier P., Choay J. In vitro spleen cell responsiveness to various analogs of MDP (N-acetylmuramyl-L-alanyl-D-isoglutamine), a synthetic immunoadjuvant, in MDP high-responder mice. Cell Immunol. 1978 Jan;35(1):173–179. doi: 10.1016/0008-8749(78)90137-5. [DOI] [PubMed] [Google Scholar]
  10. Damais C., Parant M., Chedid L. Nonspecific activation of murine spleen cells in vitro by a synthetic immunoadjuvant (N-acetyl-muramyl-L-alanyl-D-isoglutamine). Cell Immunol. 1977 Nov;34(1):49–56. doi: 10.1016/0008-8749(77)90228-3. [DOI] [PubMed] [Google Scholar]
  11. Ellouz F., Adam A., Ciorbaru R., Lederer E. Minimal structural requirements for adjuvant activity of bacterial peptidoglycan derivatives. Biochem Biophys Res Commun. 1974 Aug 19;59(4):1317–1325. doi: 10.1016/0006-291x(74)90458-6. [DOI] [PubMed] [Google Scholar]
  12. JERNE N. K., NORDIN A. A. Plaque formation in agar by single antibody-producing cells. Science. 1963 Apr 26;140(3565):405–405. [PubMed] [Google Scholar]
  13. Juy D., Chedid L. Comparison between macrophage activation and enhancement of nonspecific resistance to tumors by mycobacterial immunoadjuvants. Proc Natl Acad Sci U S A. 1975 Oct;72(10):4105–4109. doi: 10.1073/pnas.72.10.4105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kobayashi S., Fukuda T., Imada I., Fujino M., Azuma I., Yamamura Y. Novel quinonyl derivatives of muramyl dipeptide possessing potent antitumor activity. Chem Pharm Bull (Tokyo) 1979 Dec;27(12):3193–3196. doi: 10.1248/cpb.27.3193. [DOI] [PubMed] [Google Scholar]
  15. Kotani S., Watanabe Y., Kinoshita F., Shimono T., Morisaki I. Immunoadjuvant activities of synthetic N-acetyl-muramyl-peptides or -amino acids. Biken J. 1975 Jun;18(2):105–111. [PubMed] [Google Scholar]
  16. Marbrook J. Primary immune response in cultures of spleen cells. Lancet. 1967 Dec 16;2(7529):1279–1281. doi: 10.1016/s0140-6736(67)90393-5. [DOI] [PubMed] [Google Scholar]
  17. Saiki I., Uemiya M., Kusama T., Yamamura Y., Azuma I. Adjuvant activity of nocardomycoloyl derivatives of N-acetylmuramyldipeptide in mice and guinea pigs. Microbiol Immunol. 1980;24(3):265–269. doi: 10.1111/j.1348-0421.1980.tb00588.x. [DOI] [PubMed] [Google Scholar]
  18. TABACHNICK M., SOBOTKA H. Azoproteins. I. Spectrophotometric studies of amino acid azo derivatives. J Biol Chem. 1959 Jul;234(7):1726–1730. [PubMed] [Google Scholar]
  19. Taniyama T., Holden H. T. Direct augmentation of cytolytic activity of tumor-derived macrophages and macrophage cell lines by muramyl dipeptide. Cell Immunol. 1979 Dec;48(2):369–374. doi: 10.1016/0008-8749(79)90131-x. [DOI] [PubMed] [Google Scholar]
  20. Yamamura Y., Azuma I., Sugimura K., Yamawaki M., Uemiya M. Adjuvant activity of 6-O-mycoloyl-N-acetylmuramuyl-L-alanyl-D-isoglutamine. Gan. 1976 Dec;67(6):867–877. [PubMed] [Google Scholar]

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