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.
Serena LazzaroNina OgrincLieke LamontGraziella VecchioGiuseppe PappalardoRon M A HeerenPublished in: Analytical and bioanalytical chemistry (2019)
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.
Keyphrases
- mass spectrometry
- photodynamic therapy
- early stage
- ms ms
- drug discovery
- high throughput
- big data
- data analysis
- heavy metals
- high resolution
- metal organic framework
- machine learning
- nitric oxide
- energy transfer
- liquid chromatography
- fluorescence imaging
- high performance liquid chromatography
- emergency department
- single cell
- tyrosine kinase
- liquid chromatography tandem mass spectrometry
- cerebral ischemia
- subarachnoid hemorrhage
- ionic liquid
- capillary electrophoresis
- artificial intelligence
- quantum dots
- sentinel lymph node
- tandem mass spectrometry
- solid phase extraction
- visible light