Journal of Guangxi Normal University(Natural Science Edition) ›› 2012, Vol. 30 ›› Issue (3): 159-170.

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Regulation of Amantadine Hydrochloride Binding with ⅡA Subdomain of Human Serum Albumin by Fatty Acid Chains

LIANG Hong1,2   

  1. 1.Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources,Guangxi Normal University, Guilin Guangxi 541004,China;
    2.College of Chemistry and Chemical Engineering,Guangxi Normal University, Guilin Guangxi 541004,China
  • Received:2012-09-06 Online:2012-09-20 Published:2018-12-04
  • Contact: LIANG Hong(1964—),male,born in Beiliu,Guangxi,Professor of Guangxi Normal University,PhD Supervisor.E-mail:hliang@gxnu.edu.cn
  • Supported by:
    Natural Science Foundation of China (31060121,21171043);Natural Science Foundation of Guangxi (2012GXNSFCB053001)

Abstract: HSA is a major protein component of blood plasma that has been exploited to bind and transport a wide variety of endogenous and exogenous organic compounds.While anionic drugs readily associate with the ⅡA subdomain of HSA,most cationic drugs poorly associate to HSA at this subdomain.In this study,the association between cationic drugs and HSA by modifying HSA with fatty acid chains was improved.For our experiments,amantadine hydrochloride,a cationic drug with antiviral and antiparkinsonian effects were tested,the results suggest that extensive myristoylation of HSA can help stabilize the interaction between amantadine and HSA in vitro.The X-ray crystallography data further elucidates the structural basis of this regulation.Additionally,the crystallography data suggests that anionic drugs,with a functional carboxylate group,may enhance the association between amantadine and HSA by a mechanism similar to myristolation.Ultimately,the results provide critical structural insight into this novel association between cationic drugs and the HSA ⅡA subdomain,raising the tempting possibility to fully exploit the unique binding capacity of HSA's ⅡA subdomain to achieve simultaneous delivery of anionic and cationic drugs.

Key words: human serum albumin, amantadine hydrochloride, fatty acid chains, fluorescence spectrum, X-ray crystallography

CLC Number: 

  • Q512
[1] PETERS T.All about Albumin:Biochemistry,Genetics and Medical Applications[M].San Diego:Academic Press,1995.
[2] ELSADEK B,KRATZ F.Impact of albumin on drug delivery-new applications on the horizon[J].J Control Release,2012,157(1):4-28.
[3] TAHERI A,DINARVAND R,MANSOORI P,et al.Enhanced anti-tumoral activity ofmethotrexate-human serum albumin conjugated nanoparticles by targeting with luteinizing hormone-releasing hormone (LHRH) peptide[J].Int J Mol Sci,2011,12:4591-4608.
[4] NEUMANN E,FREI E,FIEHN C.Native albumin for targeted drug delivery[J].Expert Opin Drug Deliv,2010,7:915-925.
[5] CHUANG V T,KRAGH-HANSEN U,OTAGIRI M.Pharmaceutical strategies utilizing recombinant human serum albumin[J].Pharm Res,2002,19:569-577.
[6] SCHÖNFELD D L,RAVELLI R B,SKERRA A,et al.The 1.8-A crystal structure ofalpha1-acid glycoprotein (Orosomucoid) solved by UV RIP reveals the broad drug-binding activity of this human plasma lipocalin[J].J Mol Biol,2008,384:393-405.
[7] KRAGH-HANSEN U.Molecular aspects of ligand binding to serum albumin[J].Pharmacol Rev,1981,33:17-53.
[8] HE X M,CARTER D C.Atomic structure and chemistry of human serum albumin[J].Nature,1992,358:209-215.
[9] HEIN K L,KRAGH-HANSEN U,NISSEN P.Crystallographic analysis reveals a unique lidocaine binding site on human serum albumin[J].J Struct Biol,2010,171:353-360.
[10] EFTINK M R.Fluorescence quenching reactions:probing biologicalmacro-molecular structures[C]//DEWEY T G.Biophysical and Biochemical Aspects of Fluorescence Spectroscopy.New York:Plenum,1991:105-133.
[11] LAKOWICZ J R.Principle of fluorescence spectroscopy[M].3rd ed.New York:Springer,1999.
[12] LAKOWICZ J R,WEBER G.Quenching of fluorescence byoxygen.Probefor structural fluctuations in macromolec-ules[J].Biochemistry,1973,12:4161-4170.
[13] EFTINK M R.Fluorescence quenching:theory and applications[J].Topics in Fluorescence Spectroscopy,2002,2:53-126.
[14] WARE W R.Oxygen quenching of fluorescence in solution:ax experimentbl study of the diffusion process[J].J Phys Chem,1962,66:455-458.
[15] ABOU-ZIED O K,AL-SHIHI O I.Fluorescence quenching studies withproteins[J].J Am Chem Soc,2008,130:10793-10801.
[16] BHATTACHARYA A A,GRUNE T,CURRY S.Crystallographic analysis reveals common modes of binding of medium and long-chain fatty acids to human serum albumin[J].J Mol Biol,2000,303:721-732.
[17] CURRY S,MANDELKOW H,BRICK P,et al.Crystal structure of humanserum albumin complexed with fatty acid reveals an asymmetric distribution of binding sites[J].Nat Struct Biol,1998,5:827-835.
[18] DELANO W L.The Pymol Molecular Graphics System[M].San Carlos,CA:DeLano Scientific,2004.
[19] MINGHETTI P P,RUFFNER D E,DUGAICZYK A,et al.Molecular structure of thehuman albumin gene is revealed by nucleotide sequence within q11-22 of chromosome 4[J].J Biol Chem,1986,261:6747-6675.
[20] ABOU-ZIED O K,ALSHIHI O I.Characterization of subdomain ⅡA binding siteof human serum albumin in its native,unfolded,and refolded states using smallmolecular probes[J].J Am Chem Soc,2008,130:10793-10801.
[21] ZUNSZAIN P A,GHUMAN J,MCDONAGH A F,et al.Crystallographic analysis of human serum albumin complexed with 4Z,15E-bilirubin-IXalpha[J].J Mol Biol,2008,381:394-406.
[22] YAMAGUCHI S,ALDINI G,UCHIDA K,et al.Delta(12)-prostaglandin J(2) as aproduct and ligand of human ser-um albumin:formation of an unusual covalent adduct at His146[J].J Am Chem Soc,2010,132:824-832.
[23] GHUMAN J,ZUNSZAIN P A,CURRY S,et al.Structural basis of thedrug-binding specificity of human serum albumin[J].J Mol Biol,2005,353:38-52.
[24] CURRY S.Lessons from the crystallographic analysis of small molecule binding to human serum albumin[J].Drug Metab Pharmacokinet,2009,24:342-357.
[25] WAGNER S,KUFLEITNER J,AVON BRIESEN H.Nanoparticulate transportof oximes over an in vitro blood-brain barrier model[J].PloS One,2010,5:e14213.
[26] KRATZ F.Albumin as a drug carrier:design of prodrugs,drug conjugates and nanoparticles[J].Journal of Controlled Release,2008,132:171-183.
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