| Popis: |
Natural compounds are of particular interest in the development of new vaccine adjuvants. Saponins isolated from the bark of the Quillaja saponaria (QS) Molina tree have proven to be one of the strongest immunoadjuvants known to date. The lead compound from this series, QS-21, has been approved for human use after over 100 clinical trials, and can now be found in the Shingrix® vaccine (GSK). However, QS-21 has several major drawbacks: chemical instability, limited source, and demanding purification process. Therefore, the development of simplified adjuvants based on this structure is a very promising area of research. [1, 2] Muramyl dipeptide (MDP) is the smallest peptidoglycan fragment capable of inducing an immune response to the present antigen. Although MDP is toxic and pyrogenic, its lipophilic derivatives overcome those side-effects and are in clinical use, e.g. mifamurtide and murabutide.[3] In this work, the design and synthesis of a Quillaja saponin-MDP conjugate will be described. Both compounds separately, Quillaja saponin and MDP, show high immunoadjuvant activities. The active pharmacophore subunit of the QS-21 is coupled with the desmuramyl dipeptide following the principle of molecular hybridization. Based on that, it is expected that their combination in a new, single chemical entity, can lead to significant enhancement of immunoadjuvant activity due to the synergistic effect. |
