title: Chemical modification of natural human tumor necrosis factor-alpha with polyethylene glycol increases its anti-tumor potency.
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.
authors.affiliation: Faculty of Pharmaceutical Sciences, Osaka University.
authors.forename: Y
authors.initials: Y
authors.lastname: Tsutsumi
authors.forename: T
authors.initials: T
authors.lastname: Kihira
authors.forename: S
authors.initials: S
authors.lastname: Yamamoto
authors.forename: K
authors.initials: K
authors.lastname: Kubo
authors.forename: S
authors.initials: S
authors.lastname: Nakagawa
authors.forename: M
authors.initials: M
authors.lastname: Miyake
authors.forename: Y
authors.initials: Y
authors.lastname: Horisawa
authors.forename: T
authors.initials: T
authors.lastname: Kanamori
authors.forename: H
authors.initials: H
authors.lastname: Ikegami
authors.forename: T
authors.initials: T
authors.lastname: Mayumi
mesh_terms: D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: C092033:PEG-modified tumor necrosis factor-alpha; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols