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Mass-Spectrometric MRM Analysis of FDA-Approved Proteins in Plasma of Healthy Volunteers

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Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry Aims and scope Submit manuscript

Abstract—

The proteomic composition of a biological sample serves as the most important feature of a biological object, and it allows discriminating normal and pathological conditions. Targeted mass spectrometric analysis, particularly, multiple reaction monitoring (MRM) using synthetic stable isotope-labeled internal standards (SIS), is the main alternative to the ELISA method for analysis of diagnostically significant proteins. Based on the MRM results, a prototype test system has been developed; it employs the targeted mass spectrometric method for multiplex, quantitative analysis of FDA-approved proteins in whole plasma. Using this approach, it was possible to measure the content of 42 proteins in 31 samples in a concentration range spanning five orders of magnitude. The interindividual variability for 30 of the 42 registered proteins was less than 40%. The largest scatter was observed for haptoglobin (68%), immunoglobulin heavy constant delta IGHD (90%), angiotensin (72%), sex hormone-binding globulin SHBG (100%), and lipoprotein-(a) (136%). The obtained results on the concentration of proteins correlate with published data (Hortin et al., Clinical Chemistry, 2008, vol. 54, 1608) with R2 = 0.84. The developed prototype test system based on targeted mass spectrometric analysis of proteins can be considered as an alternative to methods using monoclonal antibodies.

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ACKNOWLEDGMENTS

This work was performed using the equipment of Core Facility “Human Proteome” (IBMC). Experimental protocols are available at http://proteocenter.ibmc.msk.ru

Funding

This work was supported by the Russian Science Foundation (project no. 20-15-00410).

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Authors and Affiliations

  1. Institute of Biomedical Chemistry (IBMC), ul. Pogodinskaya 10, 119121, Moscow, Russia

    S. E. Novikova, T. E. Farafonova, O. V. Tikhonova, N. A. Shushkova, M. A. Pyatnitsky, V. G. Zgoda, E. A. Ponomarenko, A. V. Lisitsa & A. I. Archakov

  2. Institute of Biomedical Problems, Russian Academy of Sciences, Khoroshevskoye sh. 76a, 123007, Moscow, Russia

    A. I. Grigoryev

  3. Federal Research Center of Nutrition Biotechnology and Food Safety, Ustinsky proezd 2/14, 109240, Moscow, Russia

    V. A. Tutelyan

Authors
  1. S. E. Novikova
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  2. T. E. Farafonova
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  3. O. V. Tikhonova
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  4. N. A. Shushkova
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  5. M. A. Pyatnitsky
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  6. V. G. Zgoda
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  7. E. A. Ponomarenko
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  8. A. V. Lisitsa
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  9. A. I. Grigoryev
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  10. V. A. Tutelyan
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  11. A. I. Archakov
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Corresponding author

Correspondence to S. E. Novikova.

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COMPLIANCE WITH ETHICAL STANDARDS

All volunteers gave written informed consent for participation in this study.

CONFLICT OF INTEREST

The authors declare that they have no conflicts of int-erest.

Supplementary materials are available in the electronic version of the article at the journal’s website (pbmc.ibmc.msk.ru).

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Translated by A. Medvedev

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Novikova, S.E., Farafonova, T.E., Tikhonova, O.V. et al. Mass-Spectrometric MRM Analysis of FDA-Approved Proteins in Plasma of Healthy Volunteers. Biochem. Moscow Suppl. Ser. B 15, 40–61 (2021). https://doi.org/10.1134/S1990750821010054

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  • DOI: https://doi.org/10.1134/S1990750821010054

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