Abstract
Interferon-α (IFNα),4 a cytokine with modulatory activities on many cell types, is useful for treating many types of cancer and infectious diseases. This study investigates whether modification of a protein, using IFNα as an example, with a lipophilic group can alter its distribution and kinetic properties in the body. Ser163 of IFNα2a was mutated to Cys to generate a free sulfhydryl group for site-specific chemical modification. IFNα2a(S163C) was conjugated by iodoacetamide derivatives of varying lengths, and the modified IFNα2a was purified by gel filtration chromatography. The biological activities of IFNα2a(S163C) and lipophilized IFNα2a(S163C) were similar to that of IFNα2a, as evidenced by their inhibitory effects on the growth of Daudi cells and on the replication of vesicular stomatitis virus in Madin-Darby bovine kidney cells. Lipophilized IFNα2a(S163C) bound to human serum albumin and cell membranes more readily than did IFNα2a. Future experiments will investigate whether lipophilized IFNα2a(S163C) has improved pharmacokinetic properties.
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Wan, L., Chang, T.W. Site-Specific Lipophilic Modification of Interferon-α. J Protein Chem 21, 371–381 (2002). https://doi.org/10.1023/A:1021134131250
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DOI: https://doi.org/10.1023/A:1021134131250