Antagonist peptides of human interferon-α2b isolated from phage display library inhibit interferon i

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:huangxinyu322
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Aim:To screen human interferon(IFN)-α2b antagonist peptides from a phagedisplayed heptapeptide library.Methods:WISH cells and polyclonal anti-IFN-α2b antibodies were used to select IFN receptor-binding peptides from a phagedisplayed heptapeptide library.The specific binding of phage clones was exam-ined by phage ELISA and immunohistochemistry.The specific binding activitiesof synthetic peptides to WISH cells were detected by competition assay.Effectsof synthetic peptides to IFN-induced antiviral activity were analyzed by evaluat-ing the cytopathic effect(CPE)using the MTT method.Results:Twenty-threepositive clones were obtained after seven rounds of selection.Ten clones wererandomly picked from the positive clones and were sequenced.The correspond-ing amino acid sequences suggested 3 groups homologous to the 3 domains ofIFN-α2b,defined by residues 24-41,43-49,and 148-158 of IFN-α2b.As theypresented as corresponding to IFN receptor-binding domains,AB loop and Ehelix,clone № 26 and 35 were chosen for further characterization and shown tobind to WISH cells.Two peptides corresponding to clone № 26 and 35,desig-nated SP-7(SLSPGLP)and FY-7(FSAPVRY)were shown to compete with GFP-IFN-α2b for binding to its receptor and to inhibit the IFN-α2b-induced antiviralactivity.Conclusion:Both IFN-α2b antagonist peptides,SP-7 and FY-7,wereable to inhibit the IFN-induced antiviral activity,and could be helpful in laying thefoundation for the molecular mechanism of the interaction between IFN and itsreceptor. Aim: To screen human interferon (IFN) -α2b antagonist peptides from a phaged displayed heptapeptide library. Methods: WISH cells and polyclonal anti-IFN-α2b antibodies were used to select IFN receptor-binding peptides from a phaged displayed heptapeptide library. The specific binding of phage clones was exam -ined by phage ELISA and immunohistochemistry. The specific binding activities of synthetic peptides to WISH cells were detected by competition assay. Effects of synthetic peptides to IFN-induced antiviral activity were analyzed by evaluat-ing the cytopathic effect (CPE) using the MTT method. Results: Twenty-three positive clones were obtained after seven rounds of selection. Ten clones were randomly picked from the positive clones and were sequenced. The correspond- ing amino acid sequences suggested 3 groups homologous to the three domains of IFN- [alpha] 2b, defined by residues 24-41, 43-49, and 148-158 of IFN-α2b.As they were rendered to IFN receptor-binding domains, AB loop and Ehelix, clone № 26 and 35 were chosen for further characterization and tob tob to WISH cells. Two peptides corresponding to clone № 26 and 35, desig-nated SP-7 (SLSPGLP) and FY-7 (FSAPVRY) were shown compete with GFP-IFN- binding to its receptor and to inhibit the IFN-α2b-induced antiviralactivity.Conclusion: Both IFN-α2b antagonist peptides, SP-7 and FY-7, were able to inhibit the IFN-induced antiviral activity, and could be helpful in laying the setting for the molecular mechanism of the interaction between IFN and its receptor.
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