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 Citations (Scopus)

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
Pages (from-to)252-260
Number of pages9
JournalJournal of Peptide Science
Volume18
Issue number4
DOIs
StatePublished - Apr 2012

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Ribonucleoproteins
Carcinoembryonic Antigen
Kupffer Cells
Circular Dichroism
Colorectal Neoplasms
Interleukin-6
Cell Surface Receptors
Molecular Dynamics Simulation
Bioactivity
Molecular dynamics
Tumors
Amino Acid Sequence
Glycoproteins
Cells
Cytokines
Neoplasm Metastasis
Amino Acids
Peptides
Liver
Computer simulation

All Science Journal Classification (ASJC) codes

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

Cite this

Hexapeptide fragment of carcinoembryonic antigen which acts as an agonist of heterogeneous ribonucleoprotein M. / Palermo, Nicholas Y.; Thomas, Peter; Murphy, Richard F.; Lovas, Sándor.

In: Journal of Peptide Science, Vol. 18, No. 4, 04.2012, p. 252-260.

Research output: Contribution to journalArticle

Palermo, Nicholas Y. ; Thomas, Peter ; Murphy, Richard F. ; Lovas, Sándor. / Hexapeptide fragment of carcinoembryonic antigen which acts as an agonist of heterogeneous ribonucleoprotein M. In: Journal of Peptide Science. 2012 ; Vol. 18, No. 4. pp. 252-260.
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