Structural Characterization by NMR of a Double Phosphorylated Chimeric Peptide Vaccine for Treatment of Alzheimer’s Disease
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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2013-04-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/18/5/4929 |
| _version_ | 1818066051371368448 |
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| author | Stefan Berger David Singer Manolis Matzapetakis Monique Richter Karla Ramírez-Gualito |
| author_facet | Stefan Berger David Singer Manolis Matzapetakis Monique Richter Karla Ramírez-Gualito |
| author_sort | Stefan Berger |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T15:01:38Z |
| format | Article |
| id | doaj.art-6a4823ba58824d0d968d7dfbb4cbbb7b |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-10T15:01:38Z |
| publishDate | 2013-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-6a4823ba58824d0d968d7dfbb4cbbb7b2022-12-22T01:44:08ZengMDPI AGMolecules1420-30492013-04-011854929494110.3390/molecules18054929Structural Characterization by NMR of a Double Phosphorylated Chimeric Peptide Vaccine for Treatment of Alzheimer’s DiseaseStefan BergerDavid SingerManolis MatzapetakisMonique RichterKarla Ramírez-GualitoRational 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.http://www.mdpi.com/1420-3049/18/5/4929NMR spectroscopyBiological Magnetic Resonance Data BankAlzheimer’s diseasepeptide vaccineB cell epitopeT cell epitopeTau proteinhyperphosphorylationMycobacterium tuberculosis |
| spellingShingle | Stefan Berger David Singer Manolis Matzapetakis Monique Richter Karla Ramírez-Gualito Structural Characterization by NMR of a Double Phosphorylated Chimeric Peptide Vaccine for Treatment of Alzheimer’s Disease Molecules NMR spectroscopy Biological Magnetic Resonance Data Bank Alzheimer’s disease peptide vaccine B cell epitope T cell epitope Tau protein hyperphosphorylation Mycobacterium tuberculosis |
| title | Structural Characterization by NMR of a Double Phosphorylated Chimeric Peptide Vaccine for Treatment of Alzheimer’s Disease |
| title_full | Structural Characterization by NMR of a Double Phosphorylated Chimeric Peptide Vaccine for Treatment of Alzheimer’s Disease |
| title_fullStr | Structural Characterization by NMR of a Double Phosphorylated Chimeric Peptide Vaccine for Treatment of Alzheimer’s Disease |
| title_full_unstemmed | Structural Characterization by NMR of a Double Phosphorylated Chimeric Peptide Vaccine for Treatment of Alzheimer’s Disease |
| title_short | Structural Characterization by NMR of a Double Phosphorylated Chimeric Peptide Vaccine for Treatment of Alzheimer’s Disease |
| title_sort | structural characterization by nmr of a double phosphorylated chimeric peptide vaccine for treatment of alzheimer s disease |
| topic | NMR spectroscopy Biological Magnetic Resonance Data Bank Alzheimer’s disease peptide vaccine B cell epitope T cell epitope Tau protein hyperphosphorylation Mycobacterium tuberculosis |
| url | http://www.mdpi.com/1420-3049/18/5/4929 |
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