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Hexapeptide fragment of carcinoembryonic antigen which acts as an agonist of heterogeneous ribonucleoprotein M
Author(s) -
Palermo Nicholas Y.,
Thomas Peter,
Murphy Richard F.,
Lovas Sándor
Publication year - 2012
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.2393
Subject(s) - carcinoembryonic antigen , chemistry , ribonucleoprotein , circular dichroism , microbiology and biotechnology , receptor , secretion , biochemistry , biology , medicine , rna , gene , cancer
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. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.