Open AccessThis article is
- freely available
Structural Characterization by NMR of a Double Phosphorylated Chimeric Peptide Vaccine for Treatment of Alzheimer’s Disease
Institute of Analytical Chemistry, University Leipzig, Johannisallee 29, Leipzig 04103, Germany
Institute of Bioanalytical Chemistry, University Leipzig, Deutscher Platz 5, Leipzig 04103, Germany
Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa. Av. da República, Oeiras 2780-157, Portugal
* Author to whom correspondence should be addressed.
Received: 7 February 2013; in revised form: 19 April 2013 / Accepted: 22 April 2013 / Published: 26 April 2013
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.
Keywords: NMR spectroscopy; Biological Magnetic Resonance Data Bank; Alzheimer’s disease; peptide vaccine; B cell epitope; T cell epitope; Tau protein; hyperphosphorylation; Mycobacterium tuberculosis
Article StatisticsClick here to load and display the download statistics.
Notes: Multiple requests from the same IP address are counted as one view.
Cite This Article
MDPI and ACS Style
Ramírez-Gualito, K.; Richter, M.; Matzapetakis, M.; Singer, D.; Berger, S. Structural Characterization by NMR of a Double Phosphorylated Chimeric Peptide Vaccine for Treatment of Alzheimer’s Disease. Molecules 2013, 18, 4929-4941.
Ramírez-Gualito K, Richter M, Matzapetakis M, Singer D, Berger S. Structural Characterization by NMR of a Double Phosphorylated Chimeric Peptide Vaccine for Treatment of Alzheimer’s Disease. Molecules. 2013; 18(5):4929-4941.
Ramírez-Gualito, Karla; Richter, Monique; Matzapetakis, Manolis; Singer, David; Berger, Stefan. 2013. "Structural Characterization by NMR of a Double Phosphorylated Chimeric Peptide Vaccine for Treatment of Alzheimer’s Disease." Molecules 18, no. 5: 4929-4941.