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Total chemical synthesis of human interferon alpha‐2b via native chemical ligation
Author(s) -
Li Jing,
Lehmann Clara,
Chen Xishan,
Romerio Fabio,
Lu Wuyuan
Publication year - 2015
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.2760
Subject(s) - peptide , proteolysis , native chemical ligation , interferon , phage display , alpha interferon , context (archaeology) , peptide library , cytokine , chemistry , amino acid , immune system , receptor , biology , biochemistry , peptide sequence , immunology , in vitro , chemical synthesis , gene , enzyme , paleontology
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. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.