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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-4-30
pubmed:abstractText
Molecular modification with polyethylene glycol (PEGylation) is an effective approach to improve protein biostability and decrease protein immunogenic activity. To create a PEGylated recombinant human acid fibroblast growth factor (rhaFGF) and improve its bio-stability, we have produced a rhaFGF mutant (rhaFGF(ser98,132)) by replacing the 98th and the 132nd cysteine residues with serine residues. The rhaFGF(ser98,132) that retains the bioactivity of rhaFGF was then site-specifically conjugated with PEG-maleimide at the 31st cysteine residue. PEGylated rhaFGF(ser98,132) has less effect than the native rhaFGF(ser98,132) on stimulating 3T3 cell proliferation in vitro; however, its biostability at a prolonged incubation under various temperatures and resistance to trypsinization were significantly enhanced, and half-life time in vivo was elongated while its immunogenicity was significantly decreased. The physiological function of PEGylated rhaFGF(ser98,132) was evaluated in a rat model of retinal ischemia/reperfusion injury, showing that in vivo supplementation of PEGylated rhaFGF(ser98,132) provided a significantly better protection than the native rhaFGF(ser98,132) against ischemia/reperfusion-induced retinal morphological changes and lipid peroxidation. The protection is probably mediated by antioxidant protective mechanisms.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0378-4274
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
170
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
146-56
pubmed:meshHeading
pubmed-meshheading:17416472-Animals, pubmed-meshheading:17416472-BALB 3T3 Cells, pubmed-meshheading:17416472-Cell Proliferation, pubmed-meshheading:17416472-Cell Survival, pubmed-meshheading:17416472-Disease Models, Animal, pubmed-meshheading:17416472-Drug Stability, pubmed-meshheading:17416472-Female, pubmed-meshheading:17416472-Fibroblast Growth Factors, pubmed-meshheading:17416472-Humans, pubmed-meshheading:17416472-Intraocular Pressure, pubmed-meshheading:17416472-Lipid Peroxidation, pubmed-meshheading:17416472-Mice, pubmed-meshheading:17416472-Mice, Inbred BALB C, pubmed-meshheading:17416472-Mutagenesis, Site-Directed, pubmed-meshheading:17416472-Polyethylene Glycols, pubmed-meshheading:17416472-Rats, pubmed-meshheading:17416472-Rats, Sprague-Dawley, pubmed-meshheading:17416472-Recombinant Proteins, pubmed-meshheading:17416472-Reperfusion Injury, pubmed-meshheading:17416472-Retina, pubmed-meshheading:17416472-Retinal Degeneration
pubmed:year
2007
pubmed:articleTitle
Enhanced protection of modified human acidic fibroblast growth factor with polyethylene glycol against ischemia/reperfusion-induced retinal damage in rats.
pubmed:affiliation
Chinese-American Research Institute for Diabetic Complications, School of Pharmaceutical Science, Wenzhou Medical College, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't