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.

The first ferrocene analogues of muramyldipeptide

“…Herein, we report MDP analogues which contain Fca instead of iGln. Having in mind that activity of previously described MDP analogues depends on their structure and stereochemistry, [13][14][15][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] we decided to prepare MDP analogues consisting of Lor D-Ala incorporated between muramic acid and Fca. For this purpose, Boc-Fca-OMe (1) was deprotected by action of gaseous HCl in EtOAc and the obtained hydrochloride salt was treated with excess of NEt 3 .…”

“Meshed-Bag Gathered-Bunch” Method for Solid-Phase Synthesis of Small Molecular Diverse Compounds

“…31 Derivatives of muramyl dipeptide that do not have a sugar moiety present have been found to display a lower pyrogenic side effect than muramyl dipeptide. 32 Therefore, the chemical synthesis and biological evaluation of more muramyl dipeptide targeted scaffolds may help us to discover new potential clinical agents with less pyrogenic side effects. Figure 4 illustrates six series of new dipeptide scaffolds that have been designed.…”

Entrapment of Peptidoglycans and Adamantyltripeptides into Liposomes: An HPLC Assay for Determination of Encapsulation Efficiency

“…Low molecular weight peptidoglycans and structurally related compounds have been characterized as putative adjuvants in numerous studies (21)(22)(23)(24)(25)(26). There has been, however, a constant endeavour to improve and prolong the immunostimulating activity of these compounds and the feasible solution was to incorporate them into liposomes.…”

“…Peptidoglycan fragments exhibit various biological activities, including immunostimulating activity that depends upon the size and composition of the peptidoglycan fragments (20). Low molecular weight peptidoglycan fragments are mostly devoid of the toxic properties characteristic for large peptidoglycans, but still retain marked immunomodulating activity (21,(23)(24)(25)(26).…”