Photo by gbohne from Berlin, DE
snake
Researchers say they have designed an antiplatelet drug based on snake venom protein that stimulates platelets to form blood clots by latching onto glycoprotein VI (GPVI), which is safer than some currently available antiplatelet drugs that target glycoproteins IIb/IIIa.
Earlier studies have shown that platelets missing GPVI do not form clots and do not lead to severe bleeding.
The researchers, therefore, designed a drug to interact with the protein glycoprotein VI.
They used trowaglerix, a protein in the venom of the Tropidolaemus wagleri snake, to block GPVI activity.
An earlier study by the team found that trowaglerix worked through GPVI antagonism.
Some currently available antiplatelet drugs are also based on protein found in snake venom but target GPIIa/IIIb instead, which leads to the side effect of bleeding.
“[W]hy that target leads to the bleeding side effect is not fully understood,” said lead co-author Tur-Fu Huang, PhD, of the National Taiwan University in Taipei.
Specifically, the team sequenced trowaglerix and found an alpha subunit that specifically targeted GPVI snaclec, which is snake venom C-type lectin protein.
They then used computational peptide design to create a series of Troα6/Troα10 peptides—a hexapeptide and decapeptide, respectively—which were derived from trowaglerix.
Mice administered this new drug, researchers report, had slower blood clot formation compared to untreated mice. In addition, the treated mice did not bleed longer than the untreated mice.
The team believes their research supports the concept that these hexa/decapeptides have therapeutic potential and can be a template for a new, safer class of antiplatelet drug with a limited bleeding side effect.
“In general, this type of molecule design does not last long in the body,” said co-author Jane Tseng, PhD, also of the National Taiwan University, “so techniques like formulation or delivery system are likely needed to extend the exposure time in the human body.”
She also indicated that the design needs to be optimized, “to ensure that the molecule only interacts with GPVI and not other proteins which can cause unintended reactions.”
The research team reported its findings in Arteriosclerosis, Thrombosis, and Vascular Biology, an American Heart Association journal.
The National Science Council of Taiwan supported the study.
