Nanosystems May Hold the Key to Surgical Recovery

Synthetic molecules that are capable of binding to heparin may eventually help patients recover from surgery without the danger of allergic reactions to drugs.

Researchers from the University of York (United Kingdom) developed the synthetic molecules, which are designed to self-assemble into nanometer-sized structures that contain multiple heparin-binding units that are capable of binding heparin just as effectively as protamine sulfate. Based on polycationic ligands, the molecules are designed to self-assemble into spherical pseudo-dendrimers that are capable of binding polyanionic heparin with affinities and binding modes similar to covalent nanostructures such as dendrimers and proteins. Binding of the ligands to heparin induces nanoscale organization of the formed nanostructures.


During surgery, patients are given heparin to thin the blood and prevent clotting. However, once surgery is finished, it is essential to remove the heparin and allow clotting so the patient can recover. Currently this is done with the drug protamine sulfate, a small, arginine rich, nuclear protein extracted from shellfish, which reverses heparin anticoagulation; the complex of heparin and protamine is then removed and broken down by the reticuloendothelial system. In patients who are allergic to fish, it can cause significant histamine release resulting in hypotension and bronchoconstriction, and also causes pulmonary hypertension. The study was published on April 19, 2011, in the Angewandte Chemie International Edition.

"Clearly there is lots of fundamental work still to be done before clinical application,” said lead author Prof. Dave Smith, PhD, from the Department of Chemistry. "However, we hope that this approach may eventually yield biocompatible and degradable heparin binders which will help surgical recovery without any of the side effects which can be caused by protamine."

Dendrimers are repeatedly branched, roughly spherical large molecules. The name comes from the Greek dendron, which translates to "tree.” Synonymous terms for dendrimer include arborols and cascade molecules. A dendrimer is typically symmetric around the core, and often adopts a spherical three-dimensional morphology.

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