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Single-molecule peptide sequencing through reverse translation of peptides into DNA - PubMed

3 hours ago
  • #single-molecule
  • #protein sequencing
  • #DNA barcoding
  • Single-molecule peptide sequencing is achieved through reverse translation of peptides into DNA.
  • The method involves a modified Edman degradation process that releases N-terminal amino acids tagged with DNA barcodes.
  • Antibody-mediated proximity extension assays identify barcoded amino acids, generating PCR-amplifiable DNA reporters.
  • High-throughput sequencing reads the DNA library, converting peptide sequences into digital DNA outputs.
  • The approach provides full sequence coverage in millions of reads and differentiates native and post-translationally modified peptides.
  • This framework redefines protein sequencing as a DNA sequencing problem, enabling high-throughput, de novo single-molecule protein sequencing.