Grant: Operating Grant

Malfunctioning of membrane proteins, known as potassium channels, is associated with a broad spectrum of cardiac arrhythmias. The exact mechanism that governs arrhythmias and how it is determined by proteins involved is yet to be understood. The focus of the current proposal is on the detailed understanding of molecular mechanisms governing formation of cardiac arrhythmias. The information obtained from theoretical and experimental studies will be used for creation of small-molecules that can restore normal function of the channel directly involved in the formation of a clinical condition known as long QT syndrome II type (LQTS-2). Another dimension of the submitted proposal is on the evaluation of cardiotoxicity of novel and existing drugs. A combined strategy to optimize drug-like compounds by targeted chemical synthesis has been developed by our group in the last three years of studies. The current submission proposes to extend this strategy to a broad range of drugs that are currently removed from the market because of their cardiotoxic and arrhythmogenic properties.