Lipophilic muramyl dipeptide-antigen conjugates as immunostimulating agents
| Autor: | Marian M. J. H. P. Willems, Dmitri V. Filippov, Jeroen D. C. Codée, Gijsbert A. van der Marel, Nico J. Meeuwenoord, Herman S. Overkleeft, Gijs G. Zom, Ferry Ossendorp, Selina Khan |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
conjugates Synthetic vaccine Immunoconjugates muramyl dipeptides medicine.medical_treatment Antigen presentation Nod2 Signaling Adaptor Protein Major histocompatibility complex Biochemistry Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound Adjuvants Immunologic Antigen NOD2 NOD2 receptor Drug Discovery medicine Antigens General Pharmacology Toxicology and Pharmaceutics innate immunity Pharmacology Innate immune system Dose-Response Relationship Drug Molecular Structure biology Organic Chemistry Dendritic Cells vaccines 030104 developmental biology chemistry biology.protein Molecular Medicine Acetylmuramyl-Alanyl-Isoglutamine Hydrophobic and Hydrophilic Interactions Adjuvant Muramyl dipeptide |
| Zdroj: | ChemMedChem, 11(2), 190-198 |
| Popis: | Muramyl dipeptide (MDP) is the smallest peptidoglycan fragment capable of triggering the innate immune system through interaction with the intracellular NOD2 receptor. To develop synthetic vaccine modalities composed of an antigenic entity (typically a small peptide) and a molecular adjuvant with well-defined activity, we previously assembled covalent MDP-antigen conjugates. Although these were found to be capable of stimulating the NOD2 receptor and were processed by dendritic cells (DCs) leading to effective antigen presentation, DC maturation-required for an apt immune response-could not be achieved with these conjugates. To improve the efficacy of these vaccine modalities, we equipped the MDP moiety with lipophilic tails, well-known modifications to enhance the immune-stimulatory activity of MDPs. Herein we report the design and synthesis of a lipophilic MDP-antigen conjugate and show that it is a promising vaccine modality capable of stimulating the NOD2 receptor, maturing DCs, and delivering antigen cargo into the MHC-I cross-presentation pathway. |
| Databáze: | OpenAIRE |
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