Abstract
Natural human tumor necrosis factor-alpha (TNF-alpha) was chemically modified with an active ester of monomethoxy polyethylene glycol (PEG). The molecular weight of PEG-modified TNF-alpha depended on the reaction time as well as the initial molar ratio of PEG to TNF-alpha. The specific activity of modified TNF-alpha was gradually reduced with increase in the degree of PEG-modification, but the plasma half-life of TNF-alpha was increased by up to 40-fold. Modified TNF-alpha showed approximately 100 times greater anti-tumor potency than unmodified TNF-alpha. Covalent attachment of PEG to TNF-alpha thus increased the bioavailability of TNF-alpha, and may facilitate its potential therapeutic use.
MeSH terms
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Animals
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Chemical Phenomena
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Chemistry, Physical
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Dose-Response Relationship, Drug
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Drug Screening Assays, Antitumor
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Drug Synergism
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Female
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Fibrosarcoma / drug therapy
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Fibrosarcoma / metabolism
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Half-Life
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Humans
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Injections, Intravenous
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Kidney / metabolism
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Mice
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Mice, Inbred BALB C
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Polyethylene Glycols / administration & dosage
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Polyethylene Glycols / chemistry
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Polyethylene Glycols / pharmacokinetics
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Polyethylene Glycols / pharmacology*
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Tumor Cells, Cultured
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Tumor Necrosis Factor-alpha / administration & dosage
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Tumor Necrosis Factor-alpha / chemistry
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Tumor Necrosis Factor-alpha / pharmacokinetics
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Tumor Necrosis Factor-alpha / pharmacology*
Substances
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PEG-modified tumor necrosis factor-alpha
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Tumor Necrosis Factor-alpha
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Polyethylene Glycols