Site-specific lipophilic modification of interferon-alpha.
Interferon-alpha (IFNalpha), 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 IFNalpha as an example, with a lipophilic group can alter its distribution and kinetic properties in the body. Ser163 of IFNalpha2a was mutated to Cys to generate a free sulfhydryl group for site-specific chemical modification. IFNalpha2a(S163C) was conjugated by iodoacetamide derivatives of varying lengths, and the modified IFNalpha2a was purified by gel filtration chromatography. The biological activities of IFNalpha2a(S163C) and lipophilized IFNalpha2a(S163C) were similar to that of IFNalpha2a, 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 IFNalpha2a(S163C) bound to human serum albumin and cell membranes more readily than did IFNalpha2a. Future experiments will investigate whether lipophilized IFNalpha2a(S163C) has improved pharmacokinetic properties.
Wan
Lei
L
Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan 300.
Chang
Tse Wen
TW
D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002460:Cell Line; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D017931:DNA Primers; D019075:Electrophoresis, Capillary; D005612:Freeze Drying; D006801:Humans; D016898:Interferon-alpha / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects / Q000254:growth & development; D014779:Virus Replication / Q000187:drug effects
D017931:DNA Primers; D016898:Interferon-alpha