PEGylation of human interferon-α2b with modified amino acids increases circulation half-life and antiproliferative activity

Abstract

Interferon-α2b (IFN-α2b) is used as a therapeutic agent against various types of cancer. In the current research, modified forms of human INF-α2b were produced to investigate the effect of amino acid substitutions on binding to the interferon receptor and antiproliferative activity. The resulting modified human IFN-α2b proteins were PEGylated to increase their in vivo circulation half-life. N-terminal PEGylation was performed using mPEG-propionaldehyde succinate (20 and 40 kDa). As a result of these modifications, IFN-α2b with modification R(23)H achieved IC50 at 0.062 ng as compared to wild type IFN-α2b (0.125 ng). PEGylation of IFN-α2b and its modified forms resulted in an increase in hydrodynamic volume and serum retention time (up to 62 h) compared to wild type IFN-α2b (4 h). However, the antiproliferative activities of PEGylated IFN against HepG2 cell line were decreased (up to 4.7%) with an increase in PEGylated IFN-α2b size as compared to the wild type.

Keywords

• IFN-α2b
• polyethylene glycol
• PEGylation
• site-directed modification
• molecular docking