BINDING STUDIES OF VALGANCICLOVIR TO HUMAN SERUM ALBUMIN BY MULTISPECTROSCOPIC TECHNIQUES
DOI:
https://doi.org/10.22159/ijpps.2018v10i10.28090Keywords:
Valganciclovir, Galancicolvir, Human Serum Albumin, Plasma Proteins, Binding ConstantsAbstract
Objective: The aim of the present study was to investigate the mode and mechanism of interactions involved towards binding of valganciclovir (VGC) with Human Serum Albumin (HSA) by spectroscopic and molecular modeling studies which can be extrapolated for the ten folds increase of bioavailability over its prodrug galanciclovir.
Methods: Herein we employed fluorescence spectroscopy for evaluating the binding constant value, site of interaction and changes in the microenvironment of HSA fluorophores. Circular dichroism (CD) and UV-Visible spectroscopy is used for conformational changes of HSA in the event of binding of valaganciclovir. These experimental studies were further corroborated with molecular modeling studies.
Results: Considerable quenching of fluorescence intensities of fluorophores in the presence of VGC showed that VGC interacts with HSA strongly with a binding constant of 4.11x104 M-1 with a free energy change of-6.26 Kcal/mol. Synchronous fluorescence and CD studies show that the microenvironment and confirmation of HSA are slightly altered in the presence of VGC. Though site marker experiments does not give any clue for identification of site, molecular docking studies showed that VGC binds to site IB of HSA.
Conclusion: The weaker dominant electrostatic interactions with minor contributions of hydrophobic interactions of VGC with HSA at site IB (catalytic domain) might be the probable reason for the relative increase of hydrolysis of VGC to galanciclovir. And moderate binding constant value with HSA implies that HSA can be able to transport VGC under physiological conditions.Â
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Spector SA, Weingeist T, Pollard RB, Dieterich DT, Samo T, Benson CA, et al. A randomized controlled study of intravenous ganciclovir therapy for cytomegalovirus peripheral retinitis in patients with AIDS. J Infect Dis 1993;168:557-63.
Foscarnet-Ganciclovir Cytomegalovirus Retinitis Trial. 4. Visual outcomes. Studies of Ocular Complications of AIDS Research Group in collaboration with the AIDS. Clinical Trials Group 1994;101:1250-61.
Palestine AG, Polis MA, De Smet MD, Baird BF, Falloon J, Kovacs JA, et al. A randomized, controlled trial of foscarnet in the treatment of cytomegalovirus retinitis in patients with AIDS. Ann Intern Med 1991;115:665-73.
Lalezari JP, Stagg RJ, Kuppermann BD, Holland GN, Kramer F, Ives DV, et al. Intravenous cidofovir for peripheral cytomegalovirus retinitis in patients with AIDS, a randomized, controlled trial. Ann Intern Med 1997;126:257-63.
Parenteral cidofovir for cytomegalovirus retinitis in patients with AIDS: the HPMPC peripheral cytomegalovirus retinitis trial. A randomized, controlled trial. Studies of Ocular Complications of AIDS Research Group in Collaboration with the AIDS Clinical Trials Group. Ann Intern Med1997;126:264-74.
Drugs.com. Auckland. Drugsite Trust online; 2009. Available from: http://www.drugs.com/pro/valcyte.html. [Last accessed on 20 Nov 2009.
Rockville MD. US department of health and human services online. Available from: http://www.aidsinfo.nih.gov/DrugsNew/DrugDetailNT.aspx?MenuItem=DrugsandSearch=Onandint_id = 271. [Last accessed on 20 Nov 2009]
Mark DP, John R, Robert MM, Carlos VP, John P, Freeman RB, et al. Valganciclovir results inimproved oral absorption of ganciclovir in liver transplant recipients. Antimicrob Agents Chemother 2000;4410:2811–5.
Ganapathy ME, Huang W, Wang H, Ganapathy V, Leibach FH. Valacyclovir: a substrate for the intestinal and renal peptide transporters PEPT1 and PEPT2. Biochem Biophys Res Commun 1998;2462:470–5.
Sinko PJ, Balimane PV. Carrier-mediated intestinal absorption of valacyclovir, the L-valyl ester prodrug of acyclovir: 1. Interactions with peptides, organic anions and organic cations in rats. Biopharm Drug Dispos 1998;194:209–17.
Aparna N, Srinivas Reddy P, Ramachary DB, Rajagopal S. Unraveling the stability of plasma proteins upon interaction of synthesized androstenedione and its derivatives-a biophysical and computational approach. ACS Omega 2017;2:6514-24.
Subramanyam R, Gollapudi A, Bonigala P, Chinnaboina M, Amooru DG. Betulinic acid binding to human serum albumin: a study of protein conformation and binding affinity. J Photochem Photobiol B 2009;94:8–12.
Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, et al. AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J Comput Chem 2009;30:2785–91.
Xu H, Yao N, Xu H, Wang T, Li G, Li Z. Characterization of the interaction between eupatorin and bovine serum albumin by spectroscopic and molecular modeling methods. Int J Mol Sci 2013;14:14185–203.
Shi JH, Pan DQ, Wang XX, Liu TT, Jiang M, Wang Q. Characterizing the binding interaction between antimalarial artemether (AMT) and bovine serum albumin (BSA): spectroscopic and molecular docking methods. J Photochem Photobiol B 2016;16:14–23.
Lakowicz JR, Principles of fluorescence spectroscopy. 2nd ed. Plenum Press; New York: 1999. p. 237.
Nooshin B, Yalda S, Mohammad Reza AK, Samira R, Shahram P, Maryam MA, et al. Spectroscopic study of the interaction between osthole and human serum albumin: identification of the possible binding site of the compound. J Lumin 2013;143:328–36.
Yuan T, Weljie AM, Vogel HJ. Tryptophan fluorescence quenching by methionine and selenomethionine residues of calmodulin: orientation of peptide and protein binding. Biochemistry 1998;37:3187–95.
Fuller CW, Miller JN. Silver medal lectures Proc Anal Div Chem Soc 1979;16:199–8.
Tang JH, Luan F, Chen XG. Binding analysis of glycyrrhetinic acid to human serum albumin: Fluorescence spectroscopy, FTIR, and molecular modeling. Bioorg Med Chem 2006;14:3210–17.
Ross PD, Subramanian S. Thermodynamics of protein association reactions: forces contributing to stability. Biochemistry 1981;20:3096–102.
Yamasaki K, GChuang VT, Maruyama T, Otagiri M. Albumin-drug interaction and its clinical implication. Biochim Biophys Acta 2013;1830:5435-43.
Sudlow G, Birkett DJ, Wade DN. The characterization of two specific drug binding sites on human serum albumin. Mol Pharmacol 1975;11:824-32.
Xu H, Liu QW, Wen YQ. Spectroscopic studies on the interaction between nicotinamide and bovine serum albumin. Spectrochim Acta Part A 2008;71:984–8.
Yeggoni DP, Subramanyam R. Binding studies of L-3,4-dihydroxyphenylalanine with human serum albumin. Mol Biosyst 2014;10:3101-10.
Ramachander M, Kalpana VS. Molecular docking of amitriptyline to ceruloplasmin, retinol-binding protein and serum albumin. Asian J Pharm Clin Res 2018;11:169-75.
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