Structural Characterization by NMR of a Double Phosphorylated Chimeric Peptide Vaccine for Treatment of Alzheimer’s Disease

Molecules

Karla Ramírez-Gualito³  Monique Richter¹  Manolis Matzapetakis²  David Singer¹ 

[1] Institute of Bioanalytical Chemistry, University Leipzig, Deutscher Platz 5, Leipzig 04103, Germany; E-Mails:;Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa. Av. da República, Oeiras 2780-157, Portugal; E-Mail:;Institute of Analytical Chemistry, University Leipzig, Johannisallee 29, Leipzig 04103, Germany; E-Mail:

关键词: NMR spectroscopy;    Biological Magnetic Resonance Data Bank;    Alzheimer’s disease;    peptide vaccine;    B cell epitope;    T cell epitope;    Tau protein;    hyperphosphorylation;    Mycobacterium tuberculosis;   

DOI  :  10.3390/molecules18054929

来源: mdpi

【 摘 要 】

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 Tau_229-237[pThr231/pSer235] and the immunomodulatory T cell epitope Ag85B_241-255 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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.