Site-specific lipophilic modification of interferon-alpha |
| |
Authors: | Wan Lei Chang Tse Wen |
| |
Institution: | (1) Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan, 300;(2) Development Center for Biotechnology, 81 Chang Hsing St., Taipei, Taiwan, 106 |
| |
Abstract: | Interferon- (IFN ),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 IFN as an example, with a lipophilic group can alter its distribution and kinetic properties in the body. Ser163 of IFN 2a was mutated to Cys to generate a free sulfhydryl group for site-specific chemical modification. IFN 2a(S163C) was conjugated by iodoacetamide derivatives of varying lengths, and the modified IFN 2a was purified by gel filtration chromatography. The biological activities of IFN 2a(S163C) and lipophilized IFN 2a(S163C) were similar to that of IFN 2a, 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 IFN 2a(S163C) bound to human serum albumin and cell membranes more readily than did IFN 2a. Future experiments will investigate whether lipophilized IFN 2a(S163C) has improved pharmacokinetic properties. |
| |
Keywords: | Interferon lipophilization pharmacokinetics site-specific modification sulfhydryl group |
本文献已被 PubMed SpringerLink 等数据库收录! |
|