Chemometric modeling of the electrochemical data to investigate proline cis/trans isomeration effect on aggregation of Tau protein

KHODARAHMI, REZA; AKBARI, VALI; MOHAMMADI, SOHEILA; FARSHADNIA, TOORAJ; RAHIMABADI, MEHDI MORADI; GOICOECHEA, HECTOR C.; JALALVAND, ALI R.

PROTEIN EXPRESSION AND PURIFICATION

ACADEMIC PRESS INC ELSEVIER SCIENCE

Año: 2021 vol. 182

1046-5928

Tau protein (Tau) is a proline-rich protein and in this work, we have developed a very interesting strategy basedon combination of electrochemistry with chemometric methods to investigate proline cis/trans isomeration effecton the Tau aggregation. To achieve this goal, the proline residues at RTPPK motif have been replaced by alanineto generate RTPAK, RTAPK and RTAAK mutants of the Tau. Then, cyclic voltammetric (CV) responses of the Tauand RTPAK, RTAPK and RTAAK as its mutants in the presence of heparin (HEP) as an anionic inducing agentwhich could trigger aggregation of the Tau were recorded at physiological conditions every hour during 12 h.Therefore, 48 data sets of titrations were obtained which were handled by chemometric methods to extract usefulinformation about aggregation of the Tau. The data were hard-modeled by EQUISPEC, SQUAD, REACTLAB andSPECFIT to extract useful quantitative information. Our results confirmed that the strength of the binding of theHEP with proteins was obeyed from Tau > RTPAK ~ RTAPK > RTAAK which confirmed that the aggregation ofthe proteins was obeyed from this order as well. Therefore, aggregation of the Tau is decreased by transformingCis isomer to Trans even in the presence of an anionic inducing agent such as HEP which may have value for thetreatment of Alzheimer?s disease.