Magnetic synthetic receptors for selective clean-up in protein biomarker quantification

Nicholas McKitterick, Frida Braathen, Magdalena Switnicka-Plak, Peter Cormack, Léon Reubsaet, Trine Grønhaug Halvorsen

Research output: Contribution to journalArticle

Abstract

Biomarker analysis by mass spectrometry (MS) can allow for the rapid quantification of low abundant biomarkers. However, the complexity of human serum is a limiting factor in MS-based bioanalysis; therefore, novel biomarker enrichment strategies are of interest, particularly if the enrichment strategies are of low cost and are easy to use. One such strategy involves the use of molecularly imprinted polymers (MIPs) as synthetic receptors for biomarker enrichment. In the present study, a magnetic solid-phase extraction (mSPE) platform, based on magnetic MIP (mMIP) sorbents, is disclosed, for use in the MS-based quantification of proteins by the bottom-up approach. Progastrin releasing peptide (ProGRP), a low abundant and clinically sensitive biomarker for small cell lung cancer (SCLC), was used to exemplify the mSPE platform. Four different mMIPs were synthesized, and an mSPE method was developed and optimized for the extraction of low concentrations of tryptic peptides from human serum. The mSPE method enabled the selective extraction of the ProGRP signature peptide, the nonapeptide NLLGLIEAK, prior to quantification of the target via LC-MS/MS. Overall, the mSPE method demonstrated its potential as a low cost, rapid, and straightforward sample preparation method, with demonstrably strong binding, acceptable recoveries, and good compatibility with MS. mMIPs are a potential low-cost alternative to current clinical methods for biomarker analysis.

Original languageEnglish
Pages (from-to)3573-3582
Number of pages10
JournalJournal of Proteome Research
Volume19
Issue number8
Early online date2 Jul 2020
DOIs
Publication statusPublished - 7 Aug 2020

Keywords

  • low abundant biomarkers
  • bottom up protein analysis
  • magnetic capture
  • molecularly imprinted polymer

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    McKitterick, N., Braathen, F., Switnicka-Plak, M., Cormack, P., Reubsaet, L., & Grønhaug Halvorsen, T. (2020). Magnetic synthetic receptors for selective clean-up in protein biomarker quantification. Journal of Proteome Research, 19(8), 3573-3582. https://doi.org/10.1021/acs.jproteome.0c00258