Researchers Identify Molecules with Interesting Anti-clotting Properties
Findings may point researchers to development of new drug therapies
Thursday, Nov. 8, 2007
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
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.
collaborated with VCU researchers Brian L. Henry, Bernhard H. Monien; and Paul
E. Bock, who is affiliated with Vanderbilt University.
About VCU and VCU Medical Center
Virginia Commonwealth University is a major, urban public research university with national and international rankings in sponsored research. Located in downtown Richmond, VCU enrolls more than 31,000 students in 226 degree and certificate programs in the arts, sciences and humanities. Sixty-seven of the programs are unique in Virginia, many of them crossing the disciplines of VCU’s 13 schools and one college. MCV Hospitals and the health sciences schools of Virginia Commonwealth University comprise VCU Medical Center, one of the nation’s leading academic medical centers. For more, see www.vcu.edu.