Binding of Dioxopromethazine Hydrochloride with Human Serum Albumin and Its Effect on the Conformation of the Protein
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Binding of Dioxopromethazine Hydrochloride with Human Serum Albumin and Its Effect on the Conformation of the Protein Ling-ling He • Xin Wang • Bin Liu • Jun Wang • Ya-guang Sun
Received: 5 September 2011 / Accepted: 28 December 2011 / Published online: 13 October 2012 Ó Springer Science+Business Media New York 2012
Abstract The interaction between dioxopromethazine hydrochloride (DPZ) and human serum albumin (HSA), in vitro, was investigated by means of fluorescence, absorption and circular dichroism (CD) spectroscopy. The results obtained from analysis of the fluorescence spectra indicate that DPZ has a strong ability to quench the intrinsic fluorescence of HSA through a static quenching mechanism. The HSA–DPZ binding distance was determined to be less than 7 nm, suggesting that energy transfer from HSA to DPZ may occur. The thermodynamic parameters of the interaction between DPZ and HSA were measured according to the van’t Hoff equation. The negative enthalpy change (DH0) and positive entropy change (DS0) values indicate that hydrophobic and electrostatic interactions play major roles in the binding between DPZ and HSA. The binding process was a favorable process in which the Gibbs energy change (DG0) is negative. The results of displacement experiments suggested that DPZ is located in site I of HSA within subdomain IIA. In addition, the results of absorption, synchronous fluorescence and CD spectra show that binding of DPZ with HSA can induce conformational changes in HSA. Keywords Dioxopromethazine hydrochloride Human serum albumin Fluorescence spectroscopy Absorption spectroscopy CD spectroscopy
1 Introduction Human serum albumin (HSA), a principal extracellular protein with a high concentration in blood plasma, plays a major role in the transport and deposition of many endogenous and L. He Y. Sun College of Applied Chemistry, Shenyang University of Chemical Technology, Shenyang 110142, China X. Wang (&) B. Liu School of Pharmaceutical Sciences, Liaoning University, Shenyang 110036, China e-mail: [email protected] J. Wang Department of Chemistry, Liaoning University, Shenyang 110036, China
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J Solution Chem (2012) 41:1853–1865
exogenous compounds [1–3]. HSA is comprised of 585 amino acid resides. Its 3D configuration is comprised of three homologous domains (I–III). Each domain is divided into two sub-domains (A, B) that contain six and four a-helices, respectively [4, 5]. Crystal structure analyses have revealed that there are two main drug-binding sites on HSA, which are located in sub-domains IIA and IIIA and named as sites I and II, respectively [5, 6]. Most compounds bind to one of these two principal binding sites. The drug–protein binding process plays a very important role in pharmacology and pharmacokinetics. It can adjust the concentration of free drugs, prolong the reaction time of the drugs, and finally influence absorption, distribution, metabolism, and externalization of the drugs [7–9] and is considered as an important factor in drug development. Dioxopromethazine hydr
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