N-[trans-2-[[2'-(acetylamino)cyclohexyl]oxy]acetyl]-L-alanyl-D-glutamic acid: a novel immunologically active carbocyclic muramyl dipeptide analogue

Abstract

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.