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Leeches provide source for cardiovascular drugs |
| TheallIneed.com/NC&T/ASBMB |
The details of this research appear in the October issue of Molecular and Cellular Proteomics, an American Society for Biochemistry and Molecular Biology journal.
Scientists have increasingly turned to blood-feeding invertebrates as a source for drugs and lead compounds to treat cardiovascular disease because these animals have evolved highly efficient mechanisms to feed on their hosts by blocking blood coagulation.
"Most heart attacks and strokes are associated with a blocked artery," explains study author Oscar Yanes. "In some cases, blood clots may cause the blockage of arteries that lead to cardiovascular disease. People with cardiovascular disease typically have an increased tendency to form blood clots, and a decreased ability to dissolve clots before they can do any damage. Therefore, compounds interrupting the blood coagulation cascade may inhibit thrombus development."
Using a strategy dubbed "Intensity Fading MALDI MS," Yanes and his colleagues at the Universitat Autònoma de Barcelona analyzed peptides and small proteins in the saliva of the medical leech Hirudo medicinalis for their ability to bind to molecules called serine proteases. This is a fast and extremely sensitive mass spectrometry-based analytical approach. Most of the coagulation factors involved in blood coagulation cascade are enzymes that belong to the serine protease family. Thus molecules that can bind to and block the action of such serine proteases can prevent coagulation.
Of the nearly 2,000 molecules the researches screened, more than 75 of them interacted specifically with the serine protease used throughout the work as target molecule. Sixteen of these binding molecules were isolated and subsequently characterized as new inhibitors that had potential to be used as drugs in treating cardiovascular disease.
The researchers chose to zero in on small proteins and peptides for several reasons, including the fact that most of the important biopharmaceutical products approved for therapeutic applications are polypeptides within a low molecular mass and because leeches have developed a battery of serine protease inhibitors in the small molecule range.
Although these new serine protease inhibitors are a long way from being used to treat cardiovascular disease, they do represent several important leads in the search for more effective anticoagulant and fibrinolytic drugs.
Encouraged by their present success, Yanes and his colleagues are planning to apply their novel approach to the screening of additional types of leeches as well as different blood sucking animals. "Leeches belong to an extensive family with a large number of species and subspecies, which have evolved highly efficient mechanisms to block blood coagulation," notes Yanes. "Considering the fast adaptation to this kind of nutrition, resulting in accelerated evolutionary selection and fixation of very specific interactions between serine protease inhibitors of the leech and proteases of the host, we think that screening additional types of leeches will lead to the discovery of very specific compounds blocking specific serine proteases of the coagulation cascade."
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