Glycoproteins play an important role in cell structure, proteolysis, cell-cell conmunications and so on. Many clinical peptide and protein drugs targeting tumor or immune diseases are also modulated by glycosylation, which affects the therapeutic efficacy and potency of the drugs. Unlike protein synthesis, glycosylation is a non-templated process, leaving it a great challenge to study the specific function of glycosylation. However, with the protein chemical synthesis, we can obtain the specifically modified glycoproteins, allowing for the follow-up function study.
In the previous work, we synthesized a human cytokine, interferon gamma (IFN-γ), with the α-selective lysine ligation protocol and validated its applicability by comparing it with a purchased recombinant wild-type IFN-γ. The synthetic sample exhibited comparable anticancer activity in vitro. The successful synthesis also establishes a basis for the further studies on generating glycosylated IFN-γ, with potentially improved efficacy and pharmacokinetic properties.