Interferon receptor recognition peptides enhance the biological potency of interferon alphas.
Based on our earlier studies that defined three strategic regions in the Type 1 interferon (IFN) molecule associated with receptor interactions and biological activity, three IFN receptor recognition peptides (IRRP) were synthesized, with amino acid sequences CLKDRHD (IRRP1), ESLLEKFYTELYQQLND (IRRP2) and YFQRITLYLTEKKYSPCA (IRRP3) and examined for biological effectiveness. In cell surface receptor binding studies, the binding capacity of cells for IFN-alpha s was increased in the presence of the IRRPs. Increased receptor occupancy resulted in increased phosphorylation-activation of the transcription factor ISGF3 and enhanced antiviral activity. The potentiating effect on IFN-induced growth inhibition was less marked. These data suggest that the IRRPs may influence the biological potency of IFN-alpha by facilitating accessibility to cell surface receptor components. The IRRPs may function to increase the number of low affinity receptor-ligand interactions necessary to initiate receptor oligomerization, thereby catalysing the formation of high affinity IFN-receptor complexes.
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Department of Microbiology, University of Toronto, Ont., Canada.
D000595:Amino Acid Sequence; D001483:Base Sequence; D001681:Biological Assay; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016898:Interferon-alpha / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D011869:Radioligand Assay; D017471:Receptors, Interferon / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C494227:IRF9 protein, human; D007370:Interferon Type I; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016898:Interferon-alpha; D010446:Peptide Fragments; D017471:Receptors, Interferon; D014157:Transcription Factors