Abstract
Studies on interactions between an anticancer alkaloid, ellipticine, and various carrier proteins in blood serum show tangible results to gain insight into the solubility and transport of the drug under physiological conditions. In this report, we extensively studied the interactions of different prototropic species of ellipticine with two prominent serum proteins namely human serum albumin (HSA) and immunoglobulin G (IgG) in their native and partially unfolded states using steady state and time resolved fluorescence spectroscopy, molecular docking and circular dichroism (CD). Both the fluorescence techniques and molecular modeling studies elucidate that only neutral species of ellipticine binds to HSA in the sudlow site II. Unlike HSA, IgG in the native state mostly binds to cationic species of ellipticine. However, in partially unfolded configuration, IgG binds to the neutral ellipticine molecules. Molecular docking studies indicate the prevalence of electrostatic interactions involving charged residues in the binding process of cationic species of ellipticine with native IgG in its F-ab region. In native conformation, the hydrophobic residues of the F-ab region are found to be buried completely by the ligand. This implies that the hydrophobic interaction will be favored by unfolding of IgG through which the hydrophobic pocket will be more accessible to neutral species of ellipticine. The circular dichroism measurements reveal that upon interaction with ellipticine, heat and acid treated HSA resumes its alpha-helical content. This conclusive comparative study on interactions of IgG and HSA with ellipticine yields the result that native HSA is responsible for transport of neutral species of ellipticine whereas IgG carries cationic ellipticine in its native form.