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New study reveals ways to better inhibit blood clots
Date:5/19/2010

Fibrin, the primary ingredient of blood clots, creates a fibrous network that stems the loss of blood at an injury site. But beyond this essential work, fibrin can also cause heart attack, stroke and tissue damage by forming clots that block blood vessels.

Fibrin forms when an enzyme removes parts of a blood protein called fibrinogen, exposing "knobs" that fit into "holes" located on both ends of fibrinogen molecules. Uncovering these knobs allows the fibrinogen molecules to attach to one another, forming a fibrin network. To inhibit unwanted fibrin formation, researchers have developed synthetic knobs to fill the holes, but the best amino acid sequence and structure for these knobs have not been well investigated.

A new study published online today in the journal Blood reveals factors that could improve the binding of synthetic fibrin knobs to holes and the structures of these knobs in solution. The study also identifies a novel synthetic knob that displays a 10-fold higher affinity for fibrinogen holes than current synthetic knobs. This research was supported by the National Institutes of Health and the Wallace H. Coulter Foundation.

"Understanding the fundamentals of this knob-hole interaction will lead to a more thorough knowledge of fibrin assembly mechanisms and allow us to establish criteria for designing superior anticoagulants with high hole affinity that can inhibit fibrin assembly," said Thomas Barker, an assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.

Barker, postdoctoral fellow Sarah Stabenfeldt and School of Computational Engineering graduate student Jared Gossett investigated the interactions between holes and short synthetic peptides modeled after real fibrin knob sequences. They focused specifically on modeling the binding interaction and characterizing the structure of the peptides in solution.

Using a technique ca
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Contact: Abby Vogel
avogel@gatech.edu
404-385-3364
Georgia Institute of Technology Research News
Source:Eurekalert  

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