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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
1995-6-6
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pubmed:abstractText |
This study was conducted to increase the anti-tumour potency and reduce the toxic side-effects of tumour necrosis factor alpha (TNF-alpha). Natural human TNF-alpha was chemically conjugated with monomethoxy polyethylene glycol (PEG) using succinimidyl coupling of lysine amino groups of TNF-alpha. The number-average molecular weight of PEG-modified TNF-alpha (PEG-TNF-alpha) increased with an increase in the reaction time and the initial molar ratio of PEG relative to TNF-alpha. The resulting modified TNF-alpha was separated into fractions of various molecular weights. The specific activity of separated PEG-TNF-alpha s relative to that of native TNF-alpha gradually decreased with an increase in the degree of PEG modification, but the plasma half-life was drastically increased with the increase in molecular weight of modified TNF-alpha. PEG-TNF-alpha s, in which 29% and 56% of lysine residues were coupled to PEG, had anti-tumour activity approximately 4 and 100 times greater than unmodified TNF-alpha in the murine Meth-A fibrosarcoma model. Extensive PEG modification did not increase its in vivo activity. A high dose of unmodified TNF-alpha induced toxic side-effects, but these were not observed with the modified TNF-alpha s. Optimal PEG modification of TNF-alpha markedly increased its bioavailability and may facilitate its potential anti-tumour therapeutic use.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/7734321-1103152,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7734321-1366535,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7734321-1379117,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7734321-1714590,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7734321-1963781,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7734321-2009860,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7734321-2043590,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7734321-2295077,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7734321-2702990,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7734321-2711380,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7734321-2720707,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7734321-3030986,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7734321-3049599,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7734321-3315281,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7734321-3493432,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7734321-3494243,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7734321-3497979,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7734321-3567916,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7734321-3594435,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7734321-3784109,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7734321-3866246,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7734321-3871770,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7734321-3932354,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7734321-393891,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7734321-6367046,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7734321-6467175,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7734321-6469400,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7734321-7007618,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7734321-7328489,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7734321-7403670
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0007-0920
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
71
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
963-8
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:7734321-Animals,
pubmed-meshheading:7734321-Antineoplastic Agents,
pubmed-meshheading:7734321-Chemistry, Pharmaceutical,
pubmed-meshheading:7734321-Dose-Response Relationship, Drug,
pubmed-meshheading:7734321-Drug Design,
pubmed-meshheading:7734321-Drug Synergism,
pubmed-meshheading:7734321-Female,
pubmed-meshheading:7734321-Fibrosarcoma,
pubmed-meshheading:7734321-Mice,
pubmed-meshheading:7734321-Mice, Inbred BALB C,
pubmed-meshheading:7734321-Neoplasm Transplantation,
pubmed-meshheading:7734321-Polyethylene Glycols,
pubmed-meshheading:7734321-Structure-Activity Relationship,
pubmed-meshheading:7734321-Tumor Necrosis Factor-alpha
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pubmed:year |
1995
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pubmed:articleTitle |
Molecular design of hybrid tumour necrosis factor alpha with polyethylene glycol increases its anti-tumour potency.
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pubmed:affiliation |
Faculty of Pharmaceutical Sciences, Osaka University, Japan.
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pubmed:publicationType |
Journal Article
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