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Chemical Modification of Natural Human Tumor Necrosis Factor-α with Polyethylene Glycol Increases Its Anti-tumor Potency |
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| Authors: | Yasuo Tsutsumi Tetsunari Kihira Susumu Yamamoto Kazuyoshi Kubo Shinsaku Nakagawa Masaharu Miyake Yoshifumi Horisawa Toshinori Kanamori Hakuo Ikegami Tadanori Mayumi |
| Affiliation: | Faculty of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565; |
| Abstract: | Natural human tumor necrosis factor-α (TNF-α) was chemically modified with an active ester of monomethoxy polyethylene glycol (PEG). The molecular weight of PEG-modified TNF-a depended on the reaction time as well as the initial molar ratio of PEG to TNF-α. The specific activity of modified TNF-α was gradually reduced with increase in the degree of PEG-modification, but the plasma half-life of TNF-α was increased by up to 40-fold. Modified TNF-α showed approximately 100 times greater anti-tumor potency than unmodified TNF-α. Covalent attachment of PEG to TNF-α thus increased the bioavailability of TNF-α, and may facilitate its potential therapeutic use. |
| Keywords: | TNF-α PEG Meth-A Chemical modification Anti-tumor potency |