Researchers at the Virginia Commonwealth University (VCU) have identified new molecules that inhibit clotting disorders.
The researchers discovered that the identified molecules binded with Thrombin (exosite II) and inhibited the mechanism of a key enzyme that played a vital role in clotting disorders which could lead to novel therapies to treat clots in the lungs and those localized deep in the body in areas such as the legs.
AdvertisementAccording to the study, Antithrombotic disorders occur when the effect of thrombin, a protein involved in coagulation, is inhibited, rendering blood unable to clot effectively. These disorders, which are considered common, could prove to be fatal. Additionally, clotting disorders arise due to complications from other diseases like cancer.
The study was designed of three highly complex molecules with unique anticoagulant properties that were prepared in the laboratory. These molecules, known as sulfated DHPs, were completely different from anticoagulants used in the clinic today including heparins, coumarins and hirudins.
The researchers established that the molecules were able to inhibit the ability of critical enzymes involved with the cascade of events involved in blood clotting. Specifically, the molecules prevented the normal action of thrombin and factor Xa, which were the critical enzymes targeted by current anticoagulant therapy.
"We have identified a new mechanism that may prevent clotting. This approach may result in new drugs for the treatment of thrombotic disorders, including pulmonary embolism, deep vein thrombosis and more," said Umesh R. Desai, Ph.D., a professor in the Department of Medicinal Chemistry at the VCU School of Pharmacy
"The molecules we have designed may possess several advantages compared to currently available anticoagulation drugs. "For example, new anti-clotting therapies may result in reduced hospital stays for patients, fewer side effects, and possibly an overall cost reduction in therapy because our molecules are likely to be synthesized in an inexpensive manner," he added.
Desai and his team have now taken up the task of investigating the unit or units in the complex molecule responsible for the anti-clotting activity.
The research was supported by grants from the National Institutes of Health and the American Heart Association National Center and appeared in the Nov. 2 issue of the Journal of Biological Chemistry.
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