title: Structural characterization by NMR of a double phosphorylated chimeric peptide vaccine for treatment of Alzheimer's disease.
abstract: Rational design of peptide vaccines becomes important for the treatment of some diseases such as Alzheimer's disease (AD) and related disorders. In this study, as part of a larger effort to explore correlations of structure and activity, we attempt to characterize the doubly phosphorylated chimeric peptide vaccine targeting a hyperphosphorylated epitope of the Tau protein. The 28-mer linear chimeric peptide consists of the double phosphorylated B cell epitope Tau₂₂₉₋₂₃₇[pThr231/pSer235] and the immunomodulatory T cell epitope Ag85B₂₄₁₋₂₅₅ originating from the well-known antigen Ag85B of the Mycobacterium tuberculosis, linked by a four amino acid sequence -GPSL-. NMR chemical shift analysis of our construct demonstrated that the synthesized peptide is essentially unfolded with a tendency to form a β-turn due to the linker. In conclusion, the -GPSL- unit presumably connects the two parts of the vaccine without transferring any structural information from one part to the other. Therefore, the double phosphorylated epitope of the Tau peptide is flexible and accessible.
authors.affiliation: Institute of Analytical Chemistry, University Leipzig, Johannisallee 29, Leipzig 04103, Germany. karamirezg@prodigy.net.mx
authors.forename: Karla
authors.initials: K
authors.lastname: Ramírez-Gualito
authors.forename: Monique
authors.initials: M
authors.lastname: Richter
authors.forename: Manolis
authors.initials: M
authors.lastname: Matzapetakis
authors.forename: David
authors.initials: D
authors.lastname: Singer
authors.forename: Stefan
authors.initials: S
authors.lastname: Berger
mesh_terms: D000217:Acyltransferases / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology; D000544:Alzheimer Disease / Q000276:immunology / Q000628:therapy; D000942:Antigens, Bacterial / Q000737:chemistry* / Q000276:immunology; D001426:Bacterial Proteins / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000737:chemistry; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology; D010766:Phosphorylation; D017433:Protein Structure, Secondary; D014612:Vaccines / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology; D016875:tau Proteins / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C054369:MAPT protein, human; D010455:Peptides; D014612:Vaccines; D016875:tau Proteins; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis