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• W3969400 abstract "Toll-like receptors (TLRs) are receptors that continuously scour their direct surroundings for pathogen associated molecular patterns (PAMPs) of bacterial, viral or fungal origin. TLRs can be found at cells that play a role in the immune system. Binding of the TLR with its corresponding ligand results in a signaling cascade, which initially activates the innate immune system and can eventually result in activation of the adaptive immune system. When used as well-defined adjuvants, their combination with antigen may increase the immunogenicity of the antigen itself. This so-called vaccine principle may lead to a desired long-lasting adaptive immune response or humoral memory. Currently a total of 11 TLRs are known in humans and their specific PAMPs are directly related to the location where the receptor resides. TLRs 1, 2, 4, 5, 6, 10 and 11 are situated on the outside of the cell membrane, where they come into direct contact with membrane components of pathogens. TLRs 3, 7, 8 and 9 can be found intracellularly and their ligands mainly consist of viral components released after cellular uptake and degradation of the invader. A large diversity of natural and synthetic TLR ligands is available. The newest generation of vaccines is based on synthetic TLR ligands having a well-defined chemical structure. The research described in this thesis is a first step towards the development of well-defined vaccines, able to trigger a controlled immune response by means of using TLR 2, 7 or 9. Discussed in detail are the synthesis and the immunological evaluation of ligands and conjugates aimed at activation of Toll-like receptors 2, 7 and 9. Some examples are the synthesis of a CpG DNA-peptide conjugate (TLR 9), a Pam3Cys-peptide conjugate (TLR 2) and a 7-hydro-8-oxo-adenine-peptide conjugate (TLR 7). After synthesis of the peptide (containing the antigen), several methods were applied to conjugate it to TLR2, 7 and 9 ligands. Resulting from the research performed, is that when well chosen, covalent coupling of a TLR ligand with an antigenic peptide results in an increase of cytokine production as well as antigen presentation, two of the most desired characteristics of a synthetic vaccine of this class. It is not unlikely, that future synthetic vaccines will be sharing these properties." @default.
• W3969400 created "2016-06-24" @default.
• W3969400 creator A5087918801 @default.
• W3969400 date "2008-11-27" @default.
• W3969400 modified "2023-09-27" @default.
• W3969400 title "Synthesis and evaluation of peptide and nucleic acid based Toll-like receptor ligands" @default.
• W3969400 hasPublicationYear "2008" @default.
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