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Peer-Reviewed Publication
J Proteome Res2025;24(8):3798-3807.August 1, 2025Journal Article

Protein Sequencing with Single Amino Acid Resolution Discerns Peptides That Discriminate Tropomyosin Proteoforms.

Natchanon Sittipongpittaya1, Kenneth A Skinner2, Erin D Jeffery1, Emily F Watts1, Gloria M Sheynkman1,3,4
1Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia 22903, United States.
2Quantum-Si Incorporated, 29 Business Park Drive, Branford, Connecticut 06405, United States.
3Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia 22903, United States.
4UVA Comprehensive Cancer Center, University of Virginia, Charlottesville, Virginia 22903, United States.

Abstract

Protein variants of the same gene─proteoforms─can have high molecular similarity yet exhibit different biological functions. Thus, the identification of unique peptides that unambiguously map to proteoforms can provide crucial biological insights. In humans, four human tropomyosin (TPM) genes produce similar proteoforms that can be challenging to distinguish with standard proteomics tools. For exa…

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