engleski

Desmuramyl peptide derivatives – synthesis and adjuvant activity

Muropeptides are fragments of unique polymers that build up the cell wall of bacteria, also called peptidoglycans. Muramyl dipeptide (MDP), N- acetylmuramyl-L-alanyl-D-isoglutamine, is the smallest structural unit of peptidoglycans showing the immunostimulating (adjuvant) activity and desmuramyl peptides are MDP analogues lacking the hydrophilic carbohydrate moiety. Numerous derivatives with different groups at C- and N- terminus of the L-Ala-D- isoGln moiety are known. Part of our earlier work was based on the synthesis of adamantyl desmuramylpeptides, where lipophilic adamanatane subunit is attached to the L-Ala-D- isoGln. Inserted adamantane group facilitates the anchoring of the peptidoglycan ʻcargoʼ to the membrane and thus exhibit enhanced immunomodulating activity which was proven in in vivo experiments. Our next object of interest refers to the influence of mannosylation on immunostimulating activity of adamantyl tripeptide. Mannose is an important sugar whose receptors, mannose receptors (MRs), present on immunocompentent cells (such as macrophages and dendritic cells) are considered to be pattern- recognition receptors binding compounds with mannose. Therefore, they are responsible for the binding mannosylated antigens or other relevant biologically active molecules containing mannose, thus affecting the immune reactions. Our current research work includes developing methodology for the stereoselective synthesis of di- and tri- antennary mannose derivatives of desmuramyl peptides where we believe that increasing of mannose subunits number will enhance strength of overall mannose – lectin interactions.

muramyldipeptide, adamant-1-yl tripeptide, D-mannose, immunostimulating activity, peptide synthesis

This work has been supported by the Croatian Science Foundation under the project " Synthesis, Structural Analysis and Biological Evaluation of Peptidomimetics and Glycoconjugates" (IP-2014-09- 7899)