Title :

Ion mobility spectrometry combined with multivariate statistical analysis: revealing the effects of a drug candidate for alzheimer's disease on a beta 1-40 peptide early assembly

Author(s) :

Lazzaro, Serena [Auteur]
Ogrinc, Nina [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Lamont, Lieke [Auteur]
Vecchio, Graziella [Auteur]
Pappalardo, Giuseppe [Auteur]
Heeren, Ron M. A. [Auteur]

Journal title :

Analytical and Bioanalytical Chemistry

Abbreviated title :

Anal. Bioanal. Chem.

Volume number :

411

Pages :

-

Publication date :

2019-09-01

ISSN :

1618-2642

Keyword(s) :

Electrospray ionization-ion mobility-mass spectrometry (ESI-IM-MS)
Amyloid beta-peptide oligomers
Alzheimer's disease (AD)
Multivariate statistical analysis (MVA)

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Inhibition of the initial stages of amyloid-beta 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 ...
Show more >Inhibition of the initial stages of amyloid-beta 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-beta1-40 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 Abeta40 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 Abeta40. 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 Abeta early assembly in vitro models at very low concentration levels of Abeta peptides.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

INSERM
Université de Lille

Collections :

• Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192

Submission date :

2022-06-15T13:59:07Z