The Study On The Synthesize And Biological Activity Of PEGylated Interferon

OBJECTIVE: To improve the stability and biological activity, interferon can be modified by activated Polyethylene glycol (PEG) with the macromolecular design. To synthesize PEGylated IFN with a series of PEG modifier, compare their differences of heat stability, enzyme stability and stability of acid base. It was detected to antiviral activities and antineoplastic activities of PEGylated IFN.METHODS: The comblike copolymers of polycarboxylic acid (CPC) were synthesized and then reacted with PEG, obtained a conjugate-- PEGylated IFN. It was determined the molecular weight of conjugate by SDS-PAGE. The difference of heat stability, enzyme stability, and stability of acid base were compared between the PEGylated IFN and IFN. Antiviral activities can be detected by the system of Hep-2 cell and VSV. MTT assay was applied to assess antineoplastic activities of PEGylated IFN.RESULTS: There were 9 kinds of PEG-IFN conjugates, which were modified by various modifier and different modifying. The results of SDS-PAGE showed that the PEG-IFN conjugates were synthesized. The molecular weight of conjugate was 60000(modified by APEO90-4000) and 40000(modified by APEO90-20000 and APEO60-2000). The heat stability, enzyme stability and stability of acid base were increased conspicuously. MTT assay showed that PEG-IFN can inhibit the proliferation of tumor cells. Inhibitory effect of the 9 kinds of PEG-IFN (marked with 1-9) was increased. The increased rates were 56.3%, 35.2%, 17.8%, 42.3%, 23.5%, 14.6%,45.5%, 26.5%, 11.4% respectively. But antiviral activity of PEG-IFN was decreased. The decreased rates were 52%, 78%, 88%, 48%, 78%, 89%, 54%, 79%, 88% respectively.CONCLUSION: The heat stability, enzyme stability and stability of acid base of products were increased conspicuously. The antiviral effect of PEGylated IFN was not more effective than which of IFN. The effect of PEG-IFN was better than the effect of IFN in inhibiting tumor cells.