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.
Kikelj
D
D
Faculty of Pharmacy, University of Ljubljana, Slovenia.
Pecar
S
S
Kotnik
V
V
Stalc
A
A
Wraber-Herzog
B
B
Simcic
S
S
Ihan
A
A
Klamfer
L
L
Povsic
L
L
Grahek
R
R
Suhadolc
E
E
Hocevar
M
M
Hönig
H
H
Rogi-Kohlenprath
R
R
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D003520:Cyclophosphamide / Q000633:toxicity; D005260:Female; D007108:Immune Tolerance / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000633:toxicity; D007202:Indicators and Reagents; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D008958:Models, Molecular; D015394:Molecular Structure; D010950:Plasma Cells / Q000187:drug effects / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013237:Stereoisomerism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000276:Adjuvants, Immunologic; D007166:Immunosuppressive Agents; D007202:Indicators and Reagents; C110783:N-trans-2-((2-(acetylamino)cyclohexyl)acetyl)-alanyl-glutamic acid; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D003520:Cyclophosphamide