The small molecule cyclocreatine (CCr) and its phosphorylated analog, PCCr, have been shown to have medically important properties in the heart and nervous system.  In order to understand how these agents interact with cell membranes at the molecular level, we have used liposomes formed from cardiac and brain tissues as a model for the lipid components. By incorporating either TEMPO or DOXYL-based spin-labels on the lipid head group and at different positions along the acyl-chain, we  monitored a range of molecular motions in the presence and absence of the drugs using electron paramagnetic resonance (EPR) spectroscopy. We varied the drug:lipid ratio, the temperature, and the position of the spin label to obtain a fuller picture of the molecular interactions. Besides discovering position and concentration-dependent differences of CCr and PCCr, we also found that the drug: liposome system is sensitive to changes in temperature.

Cyclocreatine: Membrane interactions studied by electron paramagnetic resonance spectroscopy

243rd National Meeting (2012)

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