UBC researchers have identified a range of blood platelet proteins that are modified by Nitroxyl, a chemical compound that shows great promise as a cardiovascular drug and treatment for alcoholism.
The use of advanced mass spectrometric techniques enabled UBC Chemistry associate professor Juergen Kast and colleagues to identify 10 proteins modified in response to Nitroxyl.
"Very little is known about how Nitroxyl works mechanically, and its effects are rarely linked to specific blood protein targets or to the actual chemical changes that the proteins undergo," says Kast, also with UBC's Centre for Blood Research and Biomedical Research Centre. "These results provide, for the first time, a possible mechanistic link between the compound and the physiological effects in blood platelets."
The findings were published this week in the journal Molecular and Cellular Proteomics.
Nitroxyl-releasing drugs--developed at The Johns Hopkins University in 2004--belong to a class of compounds that exhibit important pharmacological effects, including inhibition of platelet aggregation, which ultimately leads to clots. In early studies, the class of drugs also appear to play a role in protecting the cardiovascular system from additional damage during heart failure, and in restoring function to organs affected by the debilitating condition. The compound has also attracted attention as an anti-alcoholism and cancer treatment.
"Given the current excitement regarding Nitroxyl's potential as a therapeutic agent, this mass spectrometry-based approach, applicable to a single protein or to all the proteins across a cell, has great potential for studying the effects of the compound in a real-life, biologically relevant setting," notes Kast.
