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Total chemical synthesis of human interferon alpha-2b via native chemical ligation.


ABSTRACT: Interferon-alpha (IFN?) 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 IFN? in clinical practice for the treatment of several viral infections and malignancies. However, overexpression of IFN? 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 IFN? production. To that end, artificial evolution of peptides from phage display libraries represents a strategy that seeks to disrupt the interaction between IFN? 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-IFN? composed entirely of D-amino acids. Here, we describe the synthesis and biological properties of IFN?2b 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.

SUBMITTER: Li J 

PROVIDER: S-EPMC4480187 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Total chemical synthesis of human interferon alpha-2b via native chemical ligation.

Li Jing J   Lehmann Clara C   Chen Xishan X   Romerio Fabio F   Lu Wuyuan W  

Journal of peptide science : an official publication of the European Peptide Society 20150324 7


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 suppres  ...[more]

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