Sequence-independent control of peptide conformation in liposomal vaccines for targeting protein misfolding diseases
| العنوان: | Sequence-independent control of peptide conformation in liposomal vaccines for targeting protein misfolding diseases |
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| المؤلفون: | Maria Pihlgren, Andrea Pfeifer, Dorin Mlaki Ndao, Claude Nicolau, Marc Baldus, Deepak Nand, Rime Madani, David T. Hickman, María Pilar López-Deber, Luitgard Nagel-Steger, Andreas Muhs, Valérie Giriens, Annie St-Pierre, Dieter Willbold, Detlev Riesner, Alberto B. Silva, Hristina Karastaneva |
| المصدر: | Journal of Biological Chemistry, 286(16), 13966. American Society for Biochemistry and Molecular Biology Inc. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Amyloid, Protein Folding, Magnetic Resonance Spectroscopy, Protein Conformation, Lipid-anchored protein, Peptide, Biology, Biochemistry, Epitope, Protein Structure, Secondary, chemistry.chemical_compound, Mice, Protein structure, Alzheimer Disease, Animals, Humans, Benzothiazoles, Neurodegeneration, Proteostasis Deficiencies, Molecular Biology, chemistry.chemical_classification, Vaccines, Circular Dichroism, Lipopeptide, Peptide Conformation, Cell Biology, Small molecule, Protein Structure, Tertiary, Mice, Inbred C57BL, Protein Misfolding, Thiazoles, chemistry, Immunoglobulin G, Liposomes, Protein Structure and Folding, Protein folding, Female, Peptides |
| الوصف: | Synthetic peptide immunogens which mimic the conformation of a target epitope of pathological relevance offer the possibility to precisely control the immune response specificity. Here, we performed conformational analyses using a panel of peptides in order to investigate the key parameters controlling their conformation upon integration into liposomal bilayers. These revealed that both the peptide lipidation pattern, lipid anchor chain length as well as the liposome surface charge, significantly alters peptide conformation. Peptide aggregation could also be modulated post- liposome assembly by the addition of distinct small-molecule β-sheet breakers. Immunization of both mice and monkeys with a model liposomal vaccine containing β-sheet aggregated lipopeptide (Palm1-15) induced polyclonal IgG antibodies which specifically recognized β-sheet multimers over monomer or non-pathological native protein. The rational design of liposome-bound peptide immunogens with defined conformation opens up the possibility to generate vaccines against a range of protein misfolding diseases such as Alzheimer’s disease. |
| وصف الملف: | application/pdf |
| تدمد: | 1083-351X 0021-9258 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a337f57da46a893e698aab99ff2d80ecTest https://pubmed.ncbi.nlm.nih.gov/21343310Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a337f57da46a893e698aab99ff2d80ec |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1083351X 00219258 |
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