A peptide mimetic of human interferon (IFN)-beta.
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.
Sato
Atsushi
A
Pharmaceutical Research Laboratories, Toray Industries Inc., 1111, Tebiro, Kamakura, Kanagawa, 248-8555, Japan. atsato@brain.riken.go.jp
Sone
Saburo
S
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D006801:Humans; D016899:Interferon-beta / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D019151:Peptide Library; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000187:drug effects / Q000502:physiology; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; C507964:IFNAR1 protein, human; C508033:IFNAR2 protein, human; D008565:Membrane Proteins; D019151:Peptide Library; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta