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Biological Chemistry

Spotting Clotting

Detection strategy for blood clot regulator combines oligonucleotide, fluorescent probe and reversible inhibitor

by Carmen Drahl
May 23, 2011 | APPEARED IN VOLUME 89, ISSUE 21

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Credit: Angew. Chem. Int. Ed.
A DNA aptamer (black) tightly binds thrombin (green) while a reversible inhibitor (pink) keeps natural inactivators away.
Credit: Angew. Chem. Int. Ed.
A DNA aptamer (black) tightly binds thrombin (green) while a reversible inhibitor (pink) keeps natural inactivators away.

A three-molecule tag team could help physicians monitor a patient’s blood clotting during major surgeries such as hip replacements, scientists in Germany report (Angew. Chem. Int. Ed., DOI: 10.1002/anie.201007032). Excessive bleeding and excessive clotting lead to complications during surgery, so monitoring clotting could save both costs and lives. An enzyme called thrombin sits at the nexus of the complex biochemical network that controls clotting, but so far no diagnostic tests that measure thrombin activity are available. A team led by Bernd Pötzsch of the University Clinic Bonn and Günter Mayer of the University of Bonn surmised that previous thrombin testing hasn’t panned out because naturally occurring thrombin inhibitors rapidly inactivate thrombin in blood samples. So they developed a strategy that begins by adding a reversible thrombin inhibitor to a blood sample, which keeps natural inhibitors out of the picture. After attaching the inhibitor-thrombin complex to a surface via a two-pronged DNA aptamer, the team washes away the reversible inhibitor and measures the captured thrombin’s activity with a fluorescent probe. With their technique, the Bonn team kept tabs on thrombin activity in five patients undergoing hip replacements.

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