Tolerogenic modulation of the immune response by oligoglycerol- and polyglycerol-peptide conjugates
| Autor: | Alf Hamann, Christina Poulsen, Sumit Kumar, Ute Hoffmann, Jennifer Pfeil, Uta Lauer, Rainer Haag, Shilpi Gupta |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Glycerol
Ovalbumin Polymers Molecular Sequence Data Biomedical Engineering Receptors Antigen T-Cell Pharmaceutical Science Biological Availability Gene Expression Bioengineering Peptide Mice Transgenic Pharmacology T-Lymphocytes Regulatory Autoimmune Diseases Mice Structure-Activity Relationship Immune system In vivo Immune Tolerance Animals Immunologic Factors Amino Acid Sequence Molecular Targeted Therapy Cells Cultured chemistry.chemical_classification Mice Inbred BALB C Tumor Necrosis Factor-alpha Organic Chemistry Biological activity Forkhead Transcription Factors Dendritic Cells Adoptive Transfer In vitro Bioavailability chemistry Peptides Linker Biotechnology Conjugate |
| Zdroj: | Bioconjugate chemistry. 26(4) |
| ISSN: | 1520-4812 |
| Popis: | Peptide-based therapy is a promising strategy for antigen-specific immunosuppression to treat or even heal autoimmune diseases with significantly reduced adverse effects compared to conventional therapies. However, there has been no major success due to the drawbacks of native peptides, i.e., limited bioavailability. Considering the importance and limitations of peptide-based therapies for treatment of autoimmune diseases, we designed and constructed oligoglycerol (OG)- and polyglycerol (PG)-based peptide conjugates. They were evaluated for their biological activity (in vitro and in vivo), bioavailability, and tolerogenic potential. Among the OG- and PG-peptide constructs, PG-peptide constructs exhibited an extended bioavailability compared to OG-peptide constructs and unconjugated peptide. Interestingly, size, structure, and linker chemistry played a critical role for the tolerogenic capacity of the constructs. The PG-peptide construct bound via an ester linkage was the most tolerogenic conjugate, while the PG-peptide construct bound via an amide induced stronger proliferation, but also higher TNF production and lower frequencies of Foxp3(+) regulatory T-cells. Therefore, we conclude that PG-peptide conjugates bound via an ester linkage are not only promising candidates for tolerogenic vaccination, but also open a new avenue toward the application of peptides for the treatment of autoimmune diseases. |
| Databáze: | OpenAIRE |
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