Warfarin is a small molecule - often present as a mixture of R and S enantiomers - prescribed as an anticoagulant for such medical conditions as heart failure and as a preventative measure for high-risk stroke patients. Warfarin’s usefulness has led it to become the most widely prescribed oral anticoagulant and is of interest to many medical researchers. However, shortly after warfarin’s entry into a patient’s bloodstream, 99% of the drug sample binds to plasma proteins, leaving very little drug remaining active in the bloodstream. This phenomenon increases the difficulty of analyzing the free warfarin within serum samples by the use of traditional methods.
Surface plasmon resonance (SPR) can be used to overcome these difficulties. By immobilizing warfarin antibodies on a sensor chip, levels of unbound warfarin in the serum can be measured in real time, as the serum is passed over the sensor’s surface.
Additionally, the raw data from SPR can be used to calculate the adsorption energy distribution (AED), which can be used to determine more nuanced binding information, such as degree of heterogeneity of the binding, which allows researchers to narrow the range of possibilities of the drug-protein binding model. Using the AED data, researchers were able to determine that the S enantiomer binds more tightly to the serum protein than does the R conformation.
Researchers developing experimental blood clotting procedures have used SPR in conjunction with gold nanorods that act as a switch, activating and deactivating clotting. SPR has been used to detect the change in the conformation of the nanorods as they regulate the coagulation. As with the AED calculations study, new uses and applications for this technology are being discovered more and more frequently, adding to the utility of an already versatile technique.