Muramyldipeptide-based Adjuvant Development
Based on our powerful Glyco™ Vaccine Development Platform. CD BioGlyco provides you with muramyldipeptide (MDP)-based adjuvant development services by different modification strategies. We will be your indispensable assistant in adjuvant development.
MDP
MDP, N-acetylmuramyl-L-alanine-D-isoglutamine, is a glycosylated dipeptide identified from the peptidoglycan fraction of mycobacteria with adjuvant properties. MDP was discovered in 1974 to be the smallest structural unit of Freund's complete adjuvant (FCA). In 1978, MDP derivatives were used as anti-plasma parasite immune adjuvants in monkeys to obtain better results. MDPs are potent adjuvants that enhance the efficacy of drugs and vaccines by enhancing cell adhesion and surface markers necessary for antigen presentation. In addition, MDP and its derivatives also have a variety of clinical uses and therapeutic potential, such as the combined injection of murabutide (MB), a synthetic immune modulator derived from MDP, and IL-2 into Meth-A sarcoma-bearing mice, it was found that 70 % of the mice had significant tumor suppression and complete tumor regression.
Action Mechanism of MDP Adjuvant
After uptake via clathrin-mediated internalization, MDP binds and activates the innate immune receptor nucleotide-binding oligomerization domain (NOD) 2 and Toll-like receptors (TLRs) that provide synergistic co-activation. This leads to efficient activation of the master immune regulators NF-κB and mitogen-activated protein kinase (MAPK), induces the production of inflammatory cytokines, promotes dendritic cell (DC) differentiation, and enhances CD8+ T cell cross-presentation. Currently, many analogs of MDP have been used as vaccine adjuvants. For example, N-acetylglucosamine-N-acetylmuramyl-L-Ala-D-isoGlu-L-Ala-glyceroldipalmitate (DTP-GDP), when formulated as a liposomal adjuvant, alleviated human metastatic colorectal cancer and enhanced the body's humoral immunity and cellular immunity.
Fig.1 The NOD2 signaling pathway. (Ogawa, 2011)
MDP Adjuvant Development Services
In cells, MDP is detected by the cytoplasmic receptor NOD2 of the human innate immune system. Studies have shown the importance of the MDP-NOD2 pathway in activating immunity. Therefore, CD BioGlyco provides customers with adjuvant development services for MDP and its derivatives in an attempt to enhance the body's immune response. MDP is synthesized by coupling reaction of N-acetyl-D-glucosamine, lactic acid or its equivalent, and dipeptide, and we can obtain MDP analogs by chemical modification. Our methods include:
- Peptide modification
Enhance adjuvant activity by modifying peptide moieties to obtain MDP derivatives. - Sugar modification
Adjuvants with better activity are obtained by modifying lactic acid, D-glucosamine, and N-acetyl groups.
CD BioGlyco is a globally recognized leader in carbohydrate adjuvant development. We are very happy to share our knowledge and experience to help researchers better complete MDP-based adjuvant development projects. If you are interested in our services, please contact us directly.
References:
- Ogawa, C.; et al. Muramyl dipeptide and its derivatives: peptide adjuvant in immunological disorders and cancer therapy. Current bioactive compounds. 2011, 7(3):180-197.
- Pifferi, C.; et al. Natural and synthetic carbohydrate-based vaccine adjuvants and their mechanisms of action. Nature Reviews Chemistry. 2021, 5(3):197-216.
