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Ion mobility spectrometry combined with multivariate statistical analysis: revealing the effects of a drug candidate for Alzheimer’s disease on Aβ1-40 peptide early assembly

Abstract : Inhibition of the initial stages of amyloid-β peptide self-assembly is a key approach in drug development for Alzheimer's disease, in which soluble and highly neurotoxic low molecular weight oligomers are produced and aggregate in the brain over time. Here we report a high-throughput method based on ion mobility mass spectrometry and multivariate statistical analysis to rapidly select statistically significant early-stage species of amyloid-β1-40 whose formation is inhibited by a candidate theranostic agent. Using this method, we have confirmed the inhibition of a Zn-porphyrin-peptide conjugate in the early self-assembly of Aβ40 peptide. The MS/MS fragmentation patterns of the species detected in the samples containing the Zn-porphyrin-peptide conjugate suggested a porphyrin-catalyzed oxidation at Met-35(O) of Aβ40. We introduce ion mobility MS combined with multivariate statistics as a systematic approach to perform data analytics in drug discovery/amyloid research that aims at the evaluation of the inhibitory effect on the Aβ early assembly in vitro models at very low concentration levels of Aβ peptides.
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https://www.hal.inserm.fr/inserm-02941601
Contributor : Michel Salzet Connect in order to contact the contributor
Submitted on : Thursday, September 17, 2020 - 10:44:02 AM
Last modification on : Monday, September 21, 2020 - 3:13:32 PM

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Serena Lazzaro, Nina Ogrinc, Lieke Lamont, Graziella Vecchio, Giuseppe Pappalardo, et al.. Ion mobility spectrometry combined with multivariate statistical analysis: revealing the effects of a drug candidate for Alzheimer’s disease on Aβ1-40 peptide early assembly. Analytical and Bioanalytical Chemistry, Springer Verlag, 2019, 411 (24), pp.6353-6363. ⟨10.1007/s00216-019-02030-7⟩. ⟨inserm-02941601⟩

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