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. 2003 Apr 15;371(Pt 2):603–608. doi: 10.1042/BJ20020993

A peptide mimetic of human interferon (IFN)-beta.

Atsushi Sato 1, Saburo Sone 1
PMCID: PMC1223311  PMID: 12542398

Abstract

Type I interferons (IFNs) are cytokines that are used clinically as antiviral and antitumour agents. The interaction of IFNs with their heterodimeric type I IFN receptor comprised of IFNAR1 and IFNAR2 is a first step to inducing biological actions. Here, we describe the successful mimicry of IFN-beta by a peptide isolated by phage-display screening using a neutralizing anti-IFN-beta monoclonal antibody. The 15-mer peptide, designated SYR6, was shown to compete with IFN-beta for binding to type I IFN receptor in a concentration-dependent manner, and was shown to elicit antiviral activity on cultured cells. This antiviral activity was not eliminated in the presence of neutralizing monoclonal antibodies to IFN-alpha, -beta and -gamma, and a low concentration of soluble type I IFN receptor, suggesting that it was not due to IFN contamination or the induction of endogenous IFNs by SYR6. This peptide might be a potent agonist to provide a mechanism of activating heterodimeric cytokine receptors.

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Selected References

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  1. Armstrong J. A. Cytopathic effect inhibition assay for interferon: microculture plate assay. Methods Enzymol. 1981;78(Pt A):381–387. doi: 10.1016/0076-6879(81)78145-x. [DOI] [PubMed] [Google Scholar]
  2. Ballinger M. D., Shyamala V., Forrest L. D., Deuter-Reinhard M., Doyle L. V., Wang J. X., Panganiban-Lustan L., Stratton J. R., Apell G., Winter J. A. Semirational design of a potent, artificial agonist of fibroblast growth factor receptors. Nat Biotechnol. 1999 Dec;17(12):1199–1204. doi: 10.1038/70746. [DOI] [PubMed] [Google Scholar]
  3. Binétruy-Tournaire R., Demangel C., Malavaud B., Vassy R., Rouyre S., Kraemer M., Plouët J., Derbin C., Perret G., Mazié J. C. Identification of a peptide blocking vascular endothelial growth factor (VEGF)-mediated angiogenesis. EMBO J. 2000 Apr 3;19(7):1525–1533. doi: 10.1093/emboj/19.7.1525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cwirla S. E., Balasubramanian P., Duffin D. J., Wagstrom C. R., Gates C. M., Singer S. C., Davis A. M., Tansik R. L., Mattheakis L. C., Boytos C. M. Peptide agonist of the thrombopoietin receptor as potent as the natural cytokine. Science. 1997 Jun 13;276(5319):1696–1699. doi: 10.1126/science.276.5319.1696. [DOI] [PubMed] [Google Scholar]
  5. Domanski P., Witte M., Kellum M., Rubinstein M., Hackett R., Pitha P., Colamonici O. R. Cloning and expression of a long form of the beta subunit of the interferon alpha beta receptor that is required for signaling. J Biol Chem. 1995 Sep 15;270(37):21606–21611. doi: 10.1074/jbc.270.37.21606. [DOI] [PubMed] [Google Scholar]
  6. Fukumoto T., Torigoe N., Kawabata S., Murakami M., Uede T., Nishi T., Ito Y., Sugimura K. Peptide mimics of the CTLA4-binding domain stimulate T-cell proliferation. Nat Biotechnol. 1998 Mar;16(3):267–270. doi: 10.1038/nbt0398-267. [DOI] [PubMed] [Google Scholar]
  7. Hoofnagle J. H. Therapy of viral hepatitis. Digestion. 1998 Aug;59(5):563–578. doi: 10.1159/000007532. [DOI] [PubMed] [Google Scholar]
  8. Kallen K. J., Grötzinger J., Rose-John S. New perspectives on the design of cytokines and growth factors. Trends Biotechnol. 2000 Nov;18(11):455–461. doi: 10.1016/s0167-7799(00)01492-x. [DOI] [PubMed] [Google Scholar]
  9. Kimura T., Kaburaki H., Miyamoto S., Katayama J., Watanabe Y. Discovery of a novel thrombopoietin mimic agonist peptide. J Biochem. 1997 Nov;122(5):1046–1051. doi: 10.1093/oxfordjournals.jbchem.a021845. [DOI] [PubMed] [Google Scholar]
  10. Kimura T., Kaburaki H., Tsujino T., Ikeda Y., Kato H., Watanabe Y. A non-peptide compound which can mimic the effect of thrombopoietin via c-Mpl. FEBS Lett. 1998 May 29;428(3):250–254. doi: 10.1016/s0014-5793(98)00536-5. [DOI] [PubMed] [Google Scholar]
  11. Mogensen K. E., Lewerenz M., Reboul J., Lutfalla G., Uzé G. The type I interferon receptor: structure, function, and evolution of a family business. J Interferon Cytokine Res. 1999 Oct;19(10):1069–1098. doi: 10.1089/107999099313019. [DOI] [PubMed] [Google Scholar]
  12. Piehler J., Schreiber G. Biophysical analysis of the interaction of human ifnar2 expressed in E. coli with IFNalpha2. J Mol Biol. 1999 May 28;289(1):57–67. doi: 10.1006/jmbi.1999.2726. [DOI] [PubMed] [Google Scholar]
  13. Sato A., Ida N., Fukuyama M., Miwa K., Kazami J., Nakamura H. Identification from a phage display library of peptides that bind to toxic shock syndrome toxin-1 and that inhibit its binding to major histocompatibility complex (MHC) class II molecules. Biochemistry. 1996 Aug 13;35(32):10441–10447. doi: 10.1021/bi960132y. [DOI] [PubMed] [Google Scholar]
  14. Sato A., Yamamoto S., Ishihara K., Hirano T., Jingami H. Novel peptide inhibitor of ecto-ADP-ribosyl cyclase of bone marrow stromal cell antigen-1 (BST-1/CD157). Biochem J. 1999 Feb 1;337(Pt 3):491–496. [PMC free article] [PubMed] [Google Scholar]
  15. Satoh Y., Kasama K., Kuwabara M., Yimin, Diao H. Y., Nakajima H., Kohanawa M., Minagawa T. Suppression of late asthmatic response by low-dose oral administration of interferon-beta in the guinea pig model of asthma. J Interferon Cytokine Res. 1999 Aug;19(8):887–894. doi: 10.1089/107999099313415. [DOI] [PubMed] [Google Scholar]
  16. Schindler C., Darnell J. E., Jr Transcriptional responses to polypeptide ligands: the JAK-STAT pathway. Annu Rev Biochem. 1995;64:621–651. doi: 10.1146/annurev.bi.64.070195.003201. [DOI] [PubMed] [Google Scholar]
  17. Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell. 2000 Oct 13;103(2):211–225. doi: 10.1016/s0092-8674(00)00114-8. [DOI] [PubMed] [Google Scholar]
  18. Sedmak J. J., Jameson P., Grossberg S. E. Procedures for stabilization of interferons. Methods Enzymol. 1981;78(Pt A):591–595. doi: 10.1016/0076-6879(81)78173-4. [DOI] [PubMed] [Google Scholar]
  19. Smith George P., Petrenko Valery A. Phage Display. Chem Rev. 1997 Apr 1;97(2):391–410. doi: 10.1021/cr960065d. [DOI] [PubMed] [Google Scholar]
  20. Sugi M., Kato H., Fujimoto M., Utsumi J., Hosoi K., Shimizu H., Kobayashi S. Monoclonal antibody to human beta interferon: characterization and application. Hybridoma. 1987 Jun;6(3):313–320. doi: 10.1089/hyb.1987.6.313. [DOI] [PubMed] [Google Scholar]
  21. Taniguchi T., Mantei N., Schwarzstein M., Nagata S., Muramatsu M., Weissmann C. Human leukocyte and fibroblast interferons are structurally related. Nature. 1980 Jun 19;285(5766):547–549. doi: 10.1038/285547a0. [DOI] [PubMed] [Google Scholar]
  22. Tian S. S., Lamb P., King A. G., Miller S. G., Kessler L., Luengo J. I., Averill L., Johnson R. K., Gleason J. G., Pelus L. M. A small, nonpeptidyl mimic of granulocyte-colony-stimulating factor [see commetns]. Science. 1998 Jul 10;281(5374):257–259. doi: 10.1126/science.281.5374.257. [DOI] [PubMed] [Google Scholar]
  23. Tyring S. K. Interferons: biochemistry and mechanisms of action. Am J Obstet Gynecol. 1995 Apr;172(4 Pt 2):1350–1353. doi: 10.1016/0002-9378(95)90402-6. [DOI] [PubMed] [Google Scholar]
  24. Whitty A., Borysenko C. W. Small molecule cytokine mimetics. Chem Biol. 1999 Apr;6(4):R107–R118. doi: 10.1016/S1074-5521(99)80034-9. [DOI] [PubMed] [Google Scholar]
  25. Wrighton N. C., Farrell F. X., Chang R., Kashyap A. K., Barbone F. P., Mulcahy L. S., Johnson D. L., Barrett R. W., Jolliffe L. K., Dower W. J. Small peptides as potent mimetics of the protein hormone erythropoietin. Science. 1996 Jul 26;273(5274):458–464. doi: 10.1126/science.273.5274.458. [DOI] [PubMed] [Google Scholar]
  26. Yamazaki S., Kuramoto K., Matsuo E., Hosoi K., Hara M., Shimizu H. Highly sensitive enzyme immunoassay of human interferon-beta 1. J Immunoassay. 1989;10(1):57–73. doi: 10.1080/01971528908053227. [DOI] [PubMed] [Google Scholar]
  27. Yayon A., Aviezer D., Safran M., Gross J. L., Heldman Y., Cabilly S., Givol D., Katchalski-Katzir E. Isolation of peptides that inhibit binding of basic fibroblast growth factor to its receptor from a random phage-epitope library. Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10643–10647. doi: 10.1073/pnas.90.22.10643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Zhang B., Salituro G., Szalkowski D., Li Z., Zhang Y., Royo I., Vilella D., Díez M. T., Pelaez F., Ruby C. Discovery of a small molecule insulin mimetic with antidiabetic activity in mice. Science. 1999 May 7;284(5416):974–977. doi: 10.1126/science.284.5416.974. [DOI] [PubMed] [Google Scholar]

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