Probing HSA and AGP Drug‐Binding Sites by Electronic Circular Dichroism

Human blood contains a large variety of proteins serving different functions, such as blood clotting, circulatory transport of molecules (including enzymes, hormones, food constituents), defense against bacteria and viruses, and finally drug binding that attenuates the effect of dose and performs drug transport to different tissues. Once a drug is taken either orally or otherwise, it appears in blood and immediately interacts with blood proteins. This interaction is an adsorption (called binding) to protein surfaces. Drug binding results in the partitioning of drug molecules into free and bound phases, and its pharmacological significance stems from the fact that both therapeutic and toxic effects are associated with the free rather than total concentration of substances. In most cases, drug molecules are oriented to specific spots, or cavities of the protein to which they could be bound by substantial force. These spots are the binding sites classically characterized by equilibrium constants and displacement experiments brought about by standard competitors. For drug-binding ability, out of the multiplicity of blood proteins, only two have utmost importance: human serum albumin (HSA) and human α1acid glycoprotein (AGP). This chapter deals with examples casting light on the binding mechanisms of these proteins from circular dichroism spectroscopy.