Kikelj, D., Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia Pečar, S., Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia Kotnik, V., Faculty of Medicine, Inst. of Microbiology and Immunology, Korytkova 2, 1105 Ljubljana, Slovenia Štalc, A., Research and Development Division, Lek d.d., Celovška 135, 1000 Ljubljana, Slovenia Wraber-Herzog, B., Faculty of Medicine, Inst. of Microbiology and Immunology, Korytkova 2, 1105 Ljubljana, Slovenia Simčič, S., Faculty of Medicine, Inst. of Microbiology and Immunology, Korytkova 2, 1105 Ljubljana, Slovenia Ihan, A., Faculty of Medicine, Inst. of Microbiology and Immunology, Korytkova 2, 1105 Ljubljana, Slovenia Klamfer, L., Faculty of Medicine, Inst. of Microbiology and Immunology, Korytkova 2, 1105 Ljubljana, Slovenia Povšič, L., Research and Development Division, Lek d.d., Celovška 135, 1000 Ljubljana, Slovenia Grahek, R., Research and Development Division, Lek d.d., Celovška 135, 1000 Ljubljana, Slovenia Suhadolc, E., Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia Hočevar, M., Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia Hönig, H., Institute of Organic Chemistry, Technical University of Graz, Stremayrgasse 16, A-8010 Graz, Austria Rogi-Kohlenprath, R., Institute of Organic Chemistry, Technical University of Graz, Stremayrgasse 16, A-8010 Graz, Austria
A novel non-pyrogenic carbocyclic muramyl dipeptide (MDP) analogue, N- (trans-2-[[2'-(acetylamino)cyclohexyl]oxy]acetyl}-L-alanyl-D-glutamic acid, was obtained by replacement of the N-acetylmuramic acid part and the D- isoglutamine residue of the MDP molecule by a trans-2-[[2'- (acetylamino)cyclohexyl]oxy]acetyl moiety and D-glutamic acid, respectively. The title compound was selected as a promising candidate for further evaluation among several related analogues on the basis of an immunorestoration test in mice. This novel nor-MDP analogue protects mice against the immunosuppressive effect of cyclophosphamide and increases the nonspecific resistance of mice against fungal infection. It is an immunomodulator which enhances the maturation of lymphocytes B to plasma cells and increases the activity of lymphocytes B and lymphocytes T as well as that of macrophages but does not alter the number of these cells.
N-{trans-2-[[2'-(acetylamino)cyclohexyl]oxy]acetyl}-L-alanyl-D- glutamic acid: A novel immunologically active carbocyclic muramyl dipeptide analogue
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Kikelj, D., Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia Pečar, S., Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia Kotnik, V., Faculty of Medicine, Inst. of Microbiology and Immunology, Korytkova 2, 1105 Ljubljana, Slovenia Štalc, A., Research and Development Division, Lek d.d., Celovška 135, 1000 Ljubljana, Slovenia Wraber-Herzog, B., Faculty of Medicine, Inst. of Microbiology and Immunology, Korytkova 2, 1105 Ljubljana, Slovenia Simčič, S., Faculty of Medicine, Inst. of Microbiology and Immunology, Korytkova 2, 1105 Ljubljana, Slovenia Ihan, A., Faculty of Medicine, Inst. of Microbiology and Immunology, Korytkova 2, 1105 Ljubljana, Slovenia Klamfer, L., Faculty of Medicine, Inst. of Microbiology and Immunology, Korytkova 2, 1105 Ljubljana, Slovenia Povšič, L., Research and Development Division, Lek d.d., Celovška 135, 1000 Ljubljana, Slovenia Grahek, R., Research and Development Division, Lek d.d., Celovška 135, 1000 Ljubljana, Slovenia Suhadolc, E., Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia Hočevar, M., Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia Hönig, H., Institute of Organic Chemistry, Technical University of Graz, Stremayrgasse 16, A-8010 Graz, Austria Rogi-Kohlenprath, R., Institute of Organic Chemistry, Technical University of Graz, Stremayrgasse 16, A-8010 Graz, Austria
N-{trans-2-[[2'-(acetylamino)cyclohexyl]oxy]acetyl}-L-alanyl-D- glutamic acid: A novel immunologically active carbocyclic muramyl dipeptide analogue
A novel non-pyrogenic carbocyclic muramyl dipeptide (MDP) analogue, N- (trans-2-[[2'-(acetylamino)cyclohexyl]oxy]acetyl}-L-alanyl-D-glutamic acid, was obtained by replacement of the N-acetylmuramic acid part and the D- isoglutamine residue of the MDP molecule by a trans-2-[[2'- (acetylamino)cyclohexyl]oxy]acetyl moiety and D-glutamic acid, respectively. The title compound was selected as a promising candidate for further evaluation among several related analogues on the basis of an immunorestoration test in mice. This novel nor-MDP analogue protects mice against the immunosuppressive effect of cyclophosphamide and increases the nonspecific resistance of mice against fungal infection. It is an immunomodulator which enhances the maturation of lymphocytes B to plasma cells and increases the activity of lymphocytes B and lymphocytes T as well as that of macrophages but does not alter the number of these cells.