Relative Quantitation of Beta-Amyloid Peptide Isomers with Simultaneous Isomerization of Multiple Aspartic Acid Residues by Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry

Daniil G Ivanov; Maria I Indeykina; Stanislav I Pekov; Anna E Bugrova; Olga I Kechko; Adel E Iusupov; Alexey S Kononikhin; Alexander A Makarov; Eugene N Nikolaev; Igor A Popov

doi:10.1021/jasms.9b00025

Relative Quantitation of Beta-Amyloid Peptide Isomers with Simultaneous Isomerization of Multiple Aspartic Acid Residues by Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry

J Am Soc Mass Spectrom. 2020 Jan 2;31(1):164-168. doi: 10.1021/jasms.9b00025. Epub 2019 Nov 21.

Authors

Daniil G Ivanov^{1

2}, Maria I Indeykina^{1

2}, Stanislav I Pekov^{2

3}, Anna E Bugrova^{1

4}, Olga I Kechko⁵, Adel E Iusupov^{1

2}, Alexey S Kononikhin^{2

6}, Alexander A Makarov⁵, Eugene N Nikolaev⁶, Igor A Popov^{2

3

4}

Affiliations

¹ Emanuel Institute of Biochemical Physics Russian Academy of Sciences, Kosygina Street 4, 119334 Moscow, Russia.
² Moscow Institute of Physics and Technology, Institutskiy pr. 9, 141700 Dolgoprudny, Moscow Region, Russia.
³ V. L. Talrose Institute for Energy Problems of Chemical Physics, N. N. Semenov Federal Center of Chemical Physics, Russian Academy of Sciences, Moscow, Russia.
⁴ V. I. Kulakov Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Healthcare of the Russian Federation, Akademika Oparina ul. 4, 117198 Moscow, Russia.
⁵ Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova ul. 32, 119991 Moscow, Russia.
⁶ Skolkovo Institute of Science and Technology, Novaya Street 100, 143025 Skolkovo, Moscow Region, Russia.

PMID: 32881518
DOI: 10.1021/jasms.9b00025

Abstract

Matrix assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry can be used for rapid quantitation of peptides with various post-translational modifications (PTM), even if they do not shift the mass of the native peptide. Previously, it was shown that MALDI-TOF MS can be used for quantitation of isoD7 beta-amyloid 1-42 peptide. On the basis of the differences in the collision-induced dissociation fragmentation pattern of native Aβ, isoD7 Aβ, isoD23 Aβ, and isoD7_23 peptide (a di-isomerized peptide with both isomerization of D7 and D23 residues), we developed a MALDI-TOF-based method for simultaneous quantitation of all of these isoforms. Using multivariate regression for analysis of fragment MS data, the method allows the determination of the molar fractions of all of these isoforms with up to 16% error for mixtures with 2 pmol total amount of the beta-amyloid peptide.

MeSH terms

Amyloid beta-Peptides / analysis*
Amyloid beta-Peptides / chemistry*
Aspartic Acid / chemistry*
Chemical Fractionation / methods
Isomerism
Multivariate Analysis
Nonlinear Dynamics
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods*

Substances

Amyloid beta-Peptides
Aspartic Acid