Virginia Commonwealth University researchers have discovered a new mechanism to inhibit key enzymes that play a major 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.
Antithrombotic disorders occur when the effect of thrombin, a protein involved in coagulation, is inhibited, rendering blood unable to clot effectively. These disorders are considered common and can be fatal. Additionally, clotting disorders arise due to complications from other diseases like cancer. Although there are a number of anticoagulation drugs available -- heparins and warfarins -- some patients develop adverse reactions to the therapy and must be closely monitored.
In a study published in the Nov. 2 issue of the Journal of Biological Chemistry, Umesh R. Desai, Ph.D., a professor in the Department of Medicinal Chemistry at the VCU School of Pharmacy, lead investigator on the study, reported on the design of three highly complex molecules with unique anticoagulant properties that were prepared in the laboratory. According Desai, these molecules, known as sulfated DHPs, are completely different from anticoagulants used in the clinic today including heparins, coumarins and hirudins.
The team demonstrated 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 prevent the normal action of thrombin and factor Xa, which are 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 Desai.
"The molecules we have designed may possess several advantages compared to currently available anticoagulation drugs," he said.
"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."
Desai and his team are now investigating which unit or units in the complex molecule are responsible for the anti-clotting activity.
This work was supported by grants from the National Institutes of Health and the American Heart Association National Center.
Desai collaborated with VCU researchers Brian L. Henry, Bernhard H. Monien; and Paul E. Bock, who is affiliated with Vanderbilt University.
Sathya Achia-Abraham | EurekAlert!
One step closer to reality
20.04.2018 | Max-Planck-Institut für Entwicklungsbiologie
The dark side of cichlid fish: from cannibal to caregiver
20.04.2018 | Veterinärmedizinische Universität Wien
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.
Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...
In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
20.04.2018 | Physics and Astronomy
20.04.2018 | Interdisciplinary Research
20.04.2018 | Physics and Astronomy