Hexapeptide fragment of carcinoembryonic antigen which acts as an agonist of heterogeneous ribonucleoprotein M

Nicholas Y. Palermo, Peter Thomas, Richard F. Murphy, Sándor Lovas

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Colorectal cancers with metastatic potential secrete the glycoprotein carcinoembryonic antigen (CEA). CEA has been implicated in colorectal cancer metastasis by inducing Kupffer cells to produce inflammatory cytokines which, in turn, make the hepatic micro-environment ideal for tumor cell implantation. CEA binds to the heterogeneous ribonucleoprotein M (hnRNP M) which acts as a cell surface receptor in Kupffer cells. The amino acid sequence in CEA, which binds the hnRNP M receptor, is Tyr-Pro-Glu-Leu-Pro-Lys. In this study, the structure of Ac-Tyr-Pro-Glu-Leu-Pro-Lys-NH 2 (YPELPK) was investigated using electronic circular dichroism, vibrational circular dichroism, and molecular dynamics simulations. The binding of the peptide to hnRNP M was also investigated using molecular docking calculations. The biological activity of YPELPK was studied using differentiated human THP-1 cells, which express hnRNP M on their surface and secrete IL-6 when stimulated by CEA. YPELPK forms a stable polyproline-II helix and stimulates IL-6 production of THP-1 cells at micromolar concentrations.

Original languageEnglish (US)
Pages (from-to)252-260
Number of pages9
JournalJournal of Peptide Science
Volume18
Issue number4
DOIs
Publication statusPublished - Apr 1 2012

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Keywords

  • Carcinoembryonic antigen
  • HnRNP M
  • Minimal sequence
  • Molecular docking
  • Molecular dynamics
  • Replica-exchange

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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