title: Total chemical synthesis of human interferon alpha-2b via native chemical ligation.
abstract: Interferon-alpha (IFNα) is a cytokine that orchestrates innate and adaptive immune responses and potently inhibits proliferation of normal and tumor cells. These properties have warranted the use of IFNα in clinical practice for the treatment of several viral infections and malignancies. However, overexpression of IFNα leads to immunopathology observed in the context of chronic viral infections and autoimmune conditions. Thus, it is desirable to develop therapeutic approaches that aim at suppressing excessive IFNα production. To that end, artificial evolution of peptides from phage display libraries represents a strategy that seeks to disrupt the interaction between IFNα and its cell surface receptor and thus inhibit the ensuing biological effects. Mirror-image phage display that screens peptide libraries against the D-enantiomer is particularly attractive because it allows for identification of proteolysis-resistant D-peptide inhibitors. This approach, however, relies on the availability of chemically synthesized D-IFNα composed entirely of D-amino acids. Here, we describe the synthesis and biological properties of IFNα2b of 165 amino acid residues produced by native chemical ligation, which represents an important first step toward the discovery of D-peptide antagonists with potential therapeutic applications.
authors: Institute of Human Virology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD, 21201, USA.|Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.
authors: Jing
authors: J
authors: Li
authors: Institute of Human Virology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD, 21201, USA.|First Department of Internal Medicine, University of Cologne, Cologne, Germany.
authors: Clara
authors: C
authors: Lehmann
authors: Institute of Human Virology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD, 21201, USA.
authors: Xishan
authors: X
authors: Chen
authors: Institute of Human Virology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD, 21201, USA.
authors: Fabio
authors: F
authors: Romerio
authors: Institute of Human Virology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD, 21201, USA.
authors: Wuyuan
authors: W
authors: Lu
mesh_terms: D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004220:Disulfides / Q000737:chemistry; D004686:Encephalomyocarditis virus / Q000187:drug effects / Q000254:growth & development; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000138:chemical synthesis* / Q000494:pharmacology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019151:Peptide Library; D010455:Peptides / Q000138:chemical synthesis* / Q000494:pharmacology; D061251:Primary Cell Culture; D017510:Protein Folding; D011994:Recombinant Proteins / Q000138:chemical synthesis / Q000494:pharmacology; D060327:Solid-Phase Synthesis Techniques / Q000379:methods*; D013237:Stereoisomerism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology
chemical_list: D004220:Disulfides; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D019151:Peptide Library; D010455:Peptides; D011994:Recombinant Proteins
keywords: interferon; native chemical ligation; peptide synthesis; synthetic protein