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Proteomics01:33

Proteomics

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A proteome is the entire set of proteins that a cell type produces. We can study proteomes using the knowledge of genomes because genes code for mRNAs, and the mRNAs encode proteins. Although mRNA analysis is a step in the right direction, not all mRNAs are translated into proteins.
Proteomics is the study of proteomes' function. It involves the large-scale systematic study of the proteome to denote the protein complement expressed by a genome. Scientist Mark Wilkins coined the term...
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  1. Home
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  5. Chemical Sciences
  7. Macromolecular And Materials Chemistry
  9. Nanochemistry
  11. Mass Spectrometry-based Top-down Proteomics In Nanomedicine: Proteoform-specific Measurement Of Protein Corona.
  1. Home
  3. Research Domains
  5. Chemical Sciences
  7. Macromolecular And Materials Chemistry
  9. Nanochemistry
  11. Mass Spectrometry-based Top-down Proteomics In Nanomedicine: Proteoform-specific Measurement Of Protein Corona.

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Mass Spectrometry-Based Top-Down Proteomics in Nanomedicine: Proteoform-Specific Measurement of Protein Corona.

Seyed Amirhossein Sadeghi1, Ali Akbar Ashkarran2, Qianyi Wang1

  • 1Department of Chemistry, Michigan State University, 578 S Shaw Lane, East Lansing, Michigan 48824, United States.

ACS Nano
|September 14, 2024

View abstract on PubMed

Summary
This summary is machine-generated.

Top-down proteomics (TDP) precisely identifies protein variants (proteoforms) in nanoparticle protein coronas. This advanced mass spectrometry method reveals detailed protein modifications, improving nanomedicine understanding and efficacy.

Keywords:
biomarker discoverymass spectrometrynanomedicineprotein coronaproteoformtop-down proteomics

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Area of Science:

  • Proteomics
  • Nanomedicine
  • Mass Spectrometry

Background:

  • Nanoparticle (NP) protein coronas are crucial for nanomedicine interactions.
  • Conventional bottom-up proteomics (BUP) identifies proteins but not specific proteoforms.
  • Proteoform-level detail is vital for predicting nanomedicine behavior.

Purpose of the Study:

  • To pioneer a mass spectrometry-based top-down proteomics (TDP) technique for characterizing protein coronas.
  • To identify specific proteoforms and their modifications on nanoparticle surfaces.
  • To advance the understanding of nanoparticle biological identity.

Main Methods:

  • Development and application of a robust, reproducible MS-based top-down proteomics (TDP) workflow.
  • Analysis of the protein corona formed on polystyrene nanoparticles.
  • Characterization of proteoforms including post-translational modifications, cleavages, and truncations.

    • Main Results:

    • Successfully identified approximately 900 proteoforms in the nanoparticle protein corona.
    • Detected proteoforms for 48 protein biomarkers, ranging from 2 to 70 kDa.
    • Revealed detailed proteoform characteristics, including combinations of PTMs, signal peptide cleavages, and truncations, beyond BUP capabilities.

    Conclusions:

    • MS-based TDP provides unprecedented detail on protein corona composition at the proteoform level.
    • TDP significantly enhances the characterization of nanoparticle biological identity.
    • Combining TDP with BUP offers a comprehensive strategy for advancing nanomedicine diagnostics and therapeutics.