Spectroscopy and Modeling

Topics: Protein, Amino acid, Fluorescence Pages: 28 (7744 words) Published: May 8, 2013
Journal of Luminescence 130 (2010) 2476–2486

Contents lists available at ScienceDirect

Journal of Luminescence
journal homepage: www.elsevier.com/locate/jlumin

Spectroscopic and nano-molecular modeling investigation on the binary and ternary bindings of colchicine and lomefloxacin to Human serum albumin with the viewpoint of multi-drug therapy J. Chamani a,n, A. Asoodeh b, M. Homayoni-Tabrizi a, Z. Amiri Tehranizadeh c, A. Baratian c, M.R. Saberi c, M. Gharanfoli d a

Department of Biology, Faculty of Sciences, Islamic Azad University-Mashhad Branch, Mashhad, Iran Department of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad, Iran Medical Chemistry Department, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran d Department of Development Biology, Culture and Science University, Tehran, Iran b c

a r t i c l e in f o
Article history: Received 21 April 2010 Received in revised form 14 August 2010 Accepted 18 August 2010 Available online 26 August 2010 Keywords: HSA Lomefloxacin Colchicine Spectroscopy Molecular dynamic

a b s t r a c t
Combination of several drugs is often necessary especially during long-term therapy. The competitive binding drugs can cause a decrease in the amount of drug bound to protein and increase the biological active fraction of the drug. The aim of this study is to analyze the interactions of Lomefloxacin (LMF) and Colchicine (COL) with human serum albumin (HSA) and to evaluate the mechanism of simultaneous binding of LMF and COL to protein. Fluorescence analysis was used to estimate the effect of drugs on the protein fluorescence and to define the binding and quenching properties of drugsHSA complexes. The binding sites for LMF and COL were identified in tertiary structure of HSA with the use of spectrofluorescence analysis. The analysis of fluorescence quenching of HSA in the binary and ternary systems show that LMF does not affect the complex formed between COL and HSA. On the contrary, COL decreases the interaction between LMF and HSA. The results of synchronous fluorescence, resonance light scattering and circular dichroism spectra of binary and ternary systems show that binding of LMF and COL to HSA can induce micro-environmental and conformational changes in HSA. The simultaneous presence of LMF and COL in binding to HSA should be taken into account in the multidrug therapy, and necessity of using a monitoring therapy owning to the possible increase of the uncontrolled toxic effects. Molecular modeling of the possible binding sites of LMF and COL in binary and ternary systems to HSA confirms the spectroscopic results. & 2010 Elsevier B.V. All rights reserved.

1. Introduction Human serum albumin (HSA) is the most abundant carrier protein in blood circulation that can bind many endogenous and exogenous compounds e.g. fatty acids, bilirubin, prostaglandins, steroids, cholesterol, uric acid, hormones, drugs and contrasting substances reversibly, with dissociation binding constant (KD) in the range of 10 À 3–10 À 8 mol L À 1 [1]. The structure of HSA has been determined crystallographically [2,3] and discovered that it consisted of three structurally homologous, predominantly helical domains (domain I, II and III), which each domain contained two subdomains (A and B). Two principal binding sites were located in sub-domains IIA and IIIA, which are named as site I and site II, respectively. The drugs bound in site I are generally bulky heterocyclic anions with the charge situated in a central position of the molecules and that in site II are aromatic carboxylic acids with n

Corresponding author. Tel.: + 98511 8437107; fax: +98511 8424020. E-mail address: Chamani@ibb.ut.ac.ir (J. Chamani).

an extended conformation and the negative charge located at one end of the molecule [4,5]. HSA is a globular protein composed of a single polypeptide chain of 585 amino acid residues with a largely alpha-helical structure. Its amino acid sequence...
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