Linked Life Data

11368309

Source:http://linkedlifedata.com/resource/pubmed/id/11368309

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2001-5-22
pubmed:abstractText
Fibrolase, a metalloproteinase isolated from the venom of Agkistrodon contortrix contortrix (southern copperhead snake), is a direct acting fibrinolytic enzyme that has been used to digest occlusive blood clots in animal models. The snake venom enzyme directly degrades fibrin associated with platelet rich blood clots and does not rely on plasminogen activation. Rethrombosis is a serious complication that is experienced in a significant percentage of patients treated with thrombolytic agents to remove occlusive vascular thrombi. The involvement of platelets in the initiation of rethrombosis is well known. Arg-Gly-Asp-(RGD)-containing agents have been shown to inhibit rethrombosis following thrombus dissolution by plasminogen activators. In an effort to create a more effective fibrinolytic enzyme and to target the enzyme to platelet-rich thrombi, thereby decreasing the potential for rethrombosis, a chimeric derivative of fibrolase has been produced. This report describes the construction and biochemical characterization of the chimeric enzyme and an evaluation of its in vitro activities. The chimera was formed by covalently incorporating an RGD-like peptide into fibrolase. The site of peptide attachment was determined to be a single lysine residue remote from the enzymes active site. Covalent modification of fibrolase with the RGD-like peptide did not inhibit either fibrinolytic activity of the enzyme nor platelet aggregation inhibitory activity of the peptide. The chimera not only retained the same level of enzymatic activity as native fibrolase, but also acquired the ability to inhibit platelet aggregation by binding to the fibrinogen receptor (integrin alphaIIbbeta3) on platelets.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0003-9861
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
384
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
227-37
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11368309-Agkistrodon, pubmed-meshheading:11368309-Amino Acid Sequence, pubmed-meshheading:11368309-Animals, pubmed-meshheading:11368309-Binding, Competitive, pubmed-meshheading:11368309-Blood Platelets, pubmed-meshheading:11368309-Cross-Linking Reagents, pubmed-meshheading:11368309-Crotalid Venoms, pubmed-meshheading:11368309-Fibrinolysis, pubmed-meshheading:11368309-Humans, pubmed-meshheading:11368309-Kinetics, pubmed-meshheading:11368309-Metalloendopeptidases, pubmed-meshheading:11368309-Models, Molecular, pubmed-meshheading:11368309-Molecular Sequence Data, pubmed-meshheading:11368309-Oligopeptides, pubmed-meshheading:11368309-Platelet Aggregation, pubmed-meshheading:11368309-Platelet Aggregation Inhibitors, pubmed-meshheading:11368309-Recombinant Fusion Proteins, pubmed-meshheading:11368309-alpha-Macroglobulins
pubmed:year
2000
pubmed:articleTitle
Chimeric derivative of fibrolase, a fibrinolytic enzyme from southern copperhead venom, possesses inhibitory activity on platelet aggregation.
pubmed:affiliation
Department of Biochemistry and Molecular Biology and Norris Comprehensive Cancer Center, University of Southern California, Keck School of Medicine, Los Angeles 90033, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.