Search Results (3)

Muramyl dipeptide (N-acetylmuramyl-L-alanyl-D-isoglutamine, MDP) is the smallest peptidoglycan fragment able to trigger an immune response by activating the NOD2 receptor. Structural modification of MDP can lead to analogues with improved immunostimulating properties. The aim of this work was to prepare mannosylated desmuramyl peptides (ManDMP) containing lipophilic triazole substituents to study their immunomodulating activities in vivo. The adjuvant activity of the prepared compounds was evaluated in the mouse model using ovalbumin as an antigen and compared to the MDP and referent adjuvant ManDMPTAd. The obtained results confirm that the α-position of D-isoGln is the best position for the attachment of lipophilic substituents, especially adamantylethyl triazole. Compound 6c exhibited the strongest adjuvant activity, comparable to the MDP and better than referent ManDMPTAd. Full article

Muramyl dipeptide (MDP) is the smallest peptidoglycan fragment able to trigger the immune response. Structural modification of MDP can lead to the preparation of analogs with improved immunostimulant properties, including desmuramyl peptides (DMPs). The aim of this work was to prepare the desmuramyl peptide (L-Ala-D-Glu)-containing adamantyl-triazole moiety and its mannosylated derivative in order to study their immunomodulatory activities in vivo. The adjuvant activity of the prepared compounds was evaluated in a murine model using ovalbumin as an antigen, and compared to the reference adjuvant ManAdDMP. The results showed that the introduction of the lipophilic adamantyl-triazole moiety at the C-terminus of L-Ala-D-Glu contributes to the immunostimulant activity of DMP, and that mannosylation of DMP modified with adamantyl-triazole causes the amplification of its immunostimulant activity. Full article

Muramyl dipeptide (MDP, N-acetylmuramyl-l-alanyl-d-isoglutamine) is known as the smallest synthetic adjuvant molecule capable of replacing whole Mycobacteria in Freund’s adjuvant. Numerous MDP derivatives were synthesized with the aim to avoid MDP unwanted side-effects. Many of them have therapeutic potential, including clinical use. A very important parameter in the improvement of pharmacological properties of MDP is lipophilicity, e.g., it eliminates drawbacks caused by poor macrophage penetration and rapid elimination. On the other side, mannose receptors (MR), present on immunocompetent cells (such as macrophages and dendritic cells), are considered to be pattern-recognition receptors and responsible for the binding, among others, of mannosylated antigens or relevant biologically active molecules containing mannose, thus affecting the immune reactions. Up to now, our research was directed towards desmuramyl peptides which contain adamantylglycine and mannosylated adamantylglycine moieties bound to the essential part of MDP, l-Ala-d-isoGln. Here, we present the design and synthesis of novel mannosylated muropeptide analogs containing 2-aminoadamantane-2-carboxylic acid. Prepared desmuramyl peptides have lipophilic 2-aminoadamantane-2-carboxylic acid attached at the N-terminus of desmuramy dipeptide core and mannose connected to the tripeptide over a glycolyl linker. Immunostimulating activities of prepared compounds will be evaluated in the mice model using ovalbumin as an antigen and compared with previously prepared derivatives. Full article