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Inhibition protein tyrosine phosphatases by an oxovanadium glutamate complex, Na2[VO(Glu)2(CH3OH)](Glu = glutamate)

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Abstract

The insulin-sensitizing effect of vanadium complexes has been linked to their ability to inhibit protein tyrosine phosphatases (PTPs). Considering that vanadium complexes may exchange in vivo with amino acids, forming in situ vanadium–amino acid complexes, we have synthesized and characterized an oxovanadium glutamate complex, Na2[V(IV)O(Glu)2(CH3OH)]H2O (1·H2O). The complex showed potent inhibition against four human PTPs (PTP1B, TCPTP, HePTP, and SHP-1) with IC50 in the 0.21–0.37 μM ranges. Fluorescence titration studies suggest that the complex binds to PTP1B with the formation of a 2:1 complex. Enzyme kinetics analysis using Lineweaver–Burk plots indicates a typical competitive inhibition mode.

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References

  • Alal PJ, Gonneville L, Hillman M, Becker-Pasha M, Yue EW, Douty B, Wayland B, Polam P, Crawley ML, McLaughlin E, Sparks RB, Glass B, Takvorian A, Combs AP, Burn TC, Hollis GF, Wynn R (2006) Structural insights into the design of nonpeptidic isothiazolidinone-containing inhibitors of protein-tyrosine phosphatase 1B. J Biol Chem 281:38013–38021

    Article  Google Scholar 

  • Andersen JN, Jansen PG, Echwald SM, Mortensen OH, Fukada T, Vecchio RD, Tonks NK, Møller NPH (2004) A genomic perspective on protein tyrosine phosphatases: gene structure, pseudogenes, and genetic disease linkage. FASEB J 18:8–30

    Article  CAS  PubMed  Google Scholar 

  • Arena S, Benvenutis S, Bardellia A (2005) Genetic analysis of the kinome and phosphatome in cancer. Cell Mol Life Sci 62:2092–2099

    Article  CAS  PubMed  Google Scholar 

  • Byon JC, Kusari AB, Kusari J (1998) Protein-tyrosine phosphatase-1B acts as a negative regulator of insulin signal transduction. Mol Cell Biochem 182:101–108

    Article  CAS  PubMed  Google Scholar 

  • Chruscinska EL, Sanna D, Garribba E, Micera G (2008) Potentiometric, spectroscopic, electrochemical and DFT characterization of oxovanadium(IV) complexes formed by citrate and tartrates in aqueous solution at high ligand to metal molar ratios: the effects of the trigonal bipyramidal distortion in bis-chelated species and biological implications. Dalton Trans 4903–4916

  • Costa Pessoa J, Antunest JL, Vilas Boas LF, Gillard RD (1992) Oxovanadium(IV) and amino acids-V. The system l-glutamic acid + VO2+; a potentiometric and spectroscopic study. Polyhedron 11(12):1449–1461

    Article  CAS  Google Scholar 

  • Crans DC, Smee JJ, Gaidamauskas E, Yang L (2004) The chemistry and biochemistry of vanadium and the biological activities exerted by vanadium compounds. Chem Rev 104:849–902

    Article  CAS  PubMed  Google Scholar 

  • Davis CW (1938) The extent of dissociation of salts in water. part VIII. An equation for the mean ionic activity coefficient of an electrolyte in water, and a revision of the dissociation constants of some sulphates. J Chem Soc 2093–2098

  • Ding F, Zhao G, Huang J, Sun Y, Zhang L (2009) Fluorescence spectroscopic investigation of the interaction between chloramphenicol and lysozyme. Eur J Med Chem 44:4083–4089

    Article  CAS  PubMed  Google Scholar 

  • Elchebly M, Payette P, Michaliszyn E, Cromlish W, Collins S, Loy AL, Normandin D, Cheng A, Himms-Hagen J, Chan CC, Ramachandran C, Gresser MJ, Tremblay ML, Kennedy BP (1999) Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene. Science 283:1544–1548

    Article  CAS  PubMed  Google Scholar 

  • Gans P, Sabatini A, Vacca A (1985) SUPERQUAD: an improved general program for computation of formation constants from potentiometric data. J Chem Soc Dalton Trans 1195–1200

  • Gao XL, Lu LP, Zhu ML, Yuan CX, Ma JF, Fu XQ (2009) Inhibitory activities of some oxovanadium complexes with N-heterocyclic ligands against PTP1B/ALP. Acta Chim Sin 67(9):929–936

    CAS  Google Scholar 

  • Guo ML, Yang BS, Yang P (1996) Ethidium bromide as a fluorescent probe for the interaction mode between titanocene dichloride and DNA. Chin Sci Bull 41:1098–1103

    CAS  Google Scholar 

  • Gyurcsik B, Jakusch T, Kiss T (2001) Oxovanadium(IV) complexes of N-D-gluconylamino acids. J Chem Soc Dalton Trans 1053–1057

  • Henry RP, Mitchell PCH, Prue JE (1973) Hydrolysis of oxovanadium(IV) ion and stability of its complexes with 1,2-dihydroxybenzenato(2−) ion. J Chem Soc Dalton Trans 1156–1159

  • Heyliger CE, Tahiliani AG, McNeill JH (1985) Effect of vanadate on elevated blood glucose and depressed cardiac performance of diabetic rats. Science 227:1474–1477

    Article  CAS  PubMed  Google Scholar 

  • Huyer G, Liu S, Kelly J, Moffat J, Payette P, Kennedy B, Tsaprailis G, Gresser MJ, Ramachandran C (1997) Mechanism of inhibition of protein-tyrosine phosphatases by vanadate and pervanadate. J Biol Chem 272:843–851

    Article  CAS  PubMed  Google Scholar 

  • Kenner KA, Anyanwu E, Olefsky JM, Kusari J (1996) Protein-tyrosine phosphatase 1B is a negative regulator of insulin- and insulin-like growth factor-I-stimulated signalling. J Biol Chem 271:19810–19816

    Article  CAS  PubMed  Google Scholar 

  • Klaman LD, Boss O, Peroni OD, Kim JK, Martino JL, Zabolotny LM, Moghal N, Lubkin M, Kim YB, Sharpe AH, Stricker-Krongrad A, Shulman GI, Neel BG, Kahn BB (2000) Increased energy expenditure, decreased adiposity, and tissue-specific insulin sensitivity in protein-tyrosine phosphatase 1B-deficient mice. Mol Cell Biol 20:5479–5489

    Article  CAS  PubMed  Google Scholar 

  • Lide DR (2008) Dissociation constants of organic acids and bases. In: CRC handbook of chemistry and physics, 88th edn. (Internet Version). CRC Press/Taylor and Francis, Boca Raton

  • Lu LP, Gao XL, Wang SX, Liu ZW, Zhu ML, Wu Q, Xing S, Fu XQ, Guo ML. Inhibition of protein tyrosine phosphatases by vanadyl-biguanide complexes. Eur J Med Chem (submitted)

  • Maccari R, Paoli P, Ottana R, Jacomelli M, Ciurleo R, Manao G, Steindl T, Langer T, Vigorita MG, Camici G (2007) 5-Arylidene-2, 4-thiazolidinediones as inhibitors of protein tyrosine phosphatases. Bioorg Med Chem 15:5137–5149

    Article  CAS  PubMed  Google Scholar 

  • Marques APD, Dockal ER, Skrobot FC, Rosa ILV (2007) Synthesis, characterization and catalytic study of [N, N’-bis(3-ethoxysalicylidene)-m-xylylenediamine] oxovanadium(IV) complex. Inorg Chem Commun 10:255–261

    Article  CAS  Google Scholar 

  • McNeill JH, Yuen VG, Dai S, Orvig C (1995) Increased potency of vanadium using organic ligands. Mol Cell Biochem 153:175–180

    Article  CAS  PubMed  Google Scholar 

  • Mondal S, Rath SP, Rajak KK, Chakravorty A (1998) A family of (N-salicylidene-α-amino acidato) vanadate esters incorporating chelated propane-1, 3-diol and glycerol: synthesis, structure, and reaction. Inorg Chem 37(8):1713–1719

    Article  CAS  Google Scholar 

  • Mukherjee R, Donnay EG, Radomski MA, Miller C, Redfern DA, Gericke A, Damron DS, Brasch NE (2008) Vanadium–vitamin B12 bioconjugates as potential therapeutics for treating diabetes. Chem Commun 3783–3785

  • Na M, Cui L, Min BS, Bae KH, Yoo JK, Kim BY, Oh WK, Ahn JS (2006) Protein tyrosine phosphatase 1B inhibitory activity of triterpenes isolated from Astilbe Koreana. Bioorg Med Chem Lett 16:3273–3276

    Article  CAS  PubMed  Google Scholar 

  • Nxumalo F, Glover NR, Tracey AS (1998) Reactions of vanadium(V) complexes of N, N-dimethylhydroxylamine with sulfur-containing ligands: implications for protein tyrosine phosphatase inhibition. J Biol Inorg Chem 3:534–542

    Article  CAS  Google Scholar 

  • Patel RN, Soni VK, Sharma S, Shukla KK, Pandeya KB (2003) pH-metric and spectrophotometric study of oxovanadium(IV) with aspartic acid, glutamic acid and imidazoles. Oxid Commun 26:358–367

    CAS  Google Scholar 

  • Peters KG, Davis MG, Howard BW, Pokross M, Rastogi V, Diven C, Greis KD, Eby-Wilkens E, Maier M, Evdokimov A, Soper S, Genbauffe FJ (2003) Mechanism of insulin sensitization by BMOV (bis maltolato oxovanadium): unliganded vanadium(VO4) as the active component. J Inorg Biochem 96:321–330

    Article  CAS  PubMed  Google Scholar 

  • Posner BI, Faure R, Burgess JW, Bevan AP, Lachance D, Zhang-Sun G, Fantus IG, Ng JB, Hall DA, Lum BS (1994) Peroxovanadium compounds. J Biol Chem 269:4596–4604

    CAS  PubMed  Google Scholar 

  • Puius YA, Zhao Y, Sullivan M, Lawrence DS, Almo SC, Zhang ZY (1997) Identification of a second aryl phosphate-binding site in protein-tyrosine phosphatase 1B: a paradigm for inhibitor design. Proc Natl Acad Sci USA 94:13420–13425

    Article  CAS  PubMed  Google Scholar 

  • Ross PD, Subramanian S (1981) Thermodynamics of protein association reactions: forces contributing to stability. Biochemistry 20:3096–3102

    Article  CAS  PubMed  Google Scholar 

  • Saltiel AR, Kahn R (2001) Insulin signalling and the regulation of glucose and lipid metabolism. Nature 414:799–806

    Article  CAS  PubMed  Google Scholar 

  • Salmeen A, Andersen JN, Myers MP, Tonks NK, Barford D (2000) Molecular basis for the dephosphorylation of the activation segment of the insulin receptor by protein tyrosine phosphatase 1B. Mol Cell 6:1401–1412

    Article  CAS  PubMed  Google Scholar 

  • SDBS Nos 4736, 4628, and 1097; SDBSWeb: http://riodb01.ibase.aist.go.jp/sdbs/ (National Institute of Advanced Industrial Science and Technology, Accessed 9 Jan 2010)

  • Shrestha S, Bhattarai BRK, Lee H, Cho H (2007) Mono- and disalicylic acid derivatives: PTP1B inhibitors as potential anti-obesity drugs. Bioorg Med Chem 15:6535–6548

    Article  CAS  PubMed  Google Scholar 

  • Sparks RB, Polam P, Zhu W, Crawley ML, Takvorian A, McLaughlin E, Wei M, Ala PJ, Gonneville L, Taylor N, Li Y, Wynn R, Burn TC, Liu PCC, Combs AP (2007) Benzothiazole benzimidazole (S)-isothiazolidinone derivatives as protein tyrosine phosphatase-1B inhibitors. Bioorg Med Chem Lett 17:736–740

    Article  CAS  PubMed  Google Scholar 

  • Wang HY, Zhang M, Lv QL, Yue NN, Gong B (2009) Determination of berberine and the study of fluorescence quenching mechanism between berberine and enzyme-catalyzed product. Spectrochim Acta Part A 73:682–686

    Article  Google Scholar 

  • Wang QM, Lu LP, Yuan CX, Pei K, Liu ZW, Guo ML, Zhu ML (2010) Potent inhibition of protein tyrosine phosphatase 1B by copper complexes: implication to copper toxicity in biological systems. Chem Commun 46:3547–3549

    Article  CAS  Google Scholar 

  • Winter CL, Lange JS, Davis MG, Gerwe GS, Downs TR, Peters KG, Kasibhatla B (2005) A nonspecific phosphotyrosine phosphatase inhibitor, bis(maltolato)oxovanadium(IV), improves glucose tolerance and prevents diabetes in zucker diabetic fatty rats. Exp Biol Med 230:207–216

    CAS  Google Scholar 

  • Xie J, Seto CT (2007) A two stage click-based library of protein tyrosine phosphatase inhibitors. Bioorg Med Chem 15:458–473

    Article  CAS  PubMed  Google Scholar 

  • Yuan CX, Lu LP, Gao XL, Wu YB, Yue JJ, Guo ML, Li Y, Fu XQ, Zhu ML (2009) Ternary oxovanadium(IV) complexes of ono-donor schiff base and polypyridyl derivatives as protein tyrosine phosphatase inhibitors: synthesis, characterization, and biological activities. J Biol Inorg Chem 14:841–851

    Article  CAS  PubMed  Google Scholar 

  • Yuan CX, Lu LP, Wu YB, Liu ZW, Guo ML, Xing S, Fu XQ, Zhu ML (2010) Synthesis, characterization, and protein tyrosine phosphatases inhibition activities of oxovanadium(IV) complexes with schiff base and polypyridyl derivatives. J Inorg Biochem doi:10.1016/j.jinorgbio.2010.05.003

  • Zamian JR, Dockal ER, Castellano G, Oliva G (1995) Synthesis and characterization of [N, N’-ethylenebis(3- ethoxysalicylideneaminato)]oxovanadium(IV). Polyhedron 14:2411–2418

    Article  CAS  Google Scholar 

  • Zhang ZY (2001) Protein tyrosine phosphatases: prospects for therapeutics. Curr Opin Chem Biol 5:416–423

    Article  CAS  PubMed  Google Scholar 

  • Zinker BA, Rondinone CM, Trevillyan JM, Gum RJ, Clampit JE, Waring JF, Xie N, Wilcox D, Jacobson P, Frost L, Kroeger PE, Reilly RM, Koterski S, Opgenorth TJ, Ulrich RG, Crosby S, Butler M, Murray SF, McKay RA, Bhanot S, Monia BP, Jirousek MR (2002) PTP1B antisense oligonucleotide lowers PTP1B protein, normalizes blood glucose, and improves insulin sensitivity in diabetic mice. Proc Natl Acad Sci USA 99:11357–11362

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was financially supported by the National Natural Science Foundation of China (Grant no. 20471033), the China Scholarship Council, the Province Natural Science Foundation of Shanxi Province of China (Grant nos. 20051013, 2010011011-2), the Overseas Returned Scholar Foundation of Shanxi Province of China in 2008 and the University of Massachusetts, Dartmouth, USA.

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Authors and Affiliations

  1. Institute of Molecular Science, Key Laboratory of Chemical Biology and Molecular Engineering of the Education Ministry, Shanxi University, Taiyuan, 030006, Shanxi, People’s Republic of China

    Liping Lu, Sulian Wang & Miaoli Zhu

  2. Department of Chemistry and Biochemistry, University of Massachusetts, Dartmouth, 02747, MA, USA

    Zhiwei Liu & Maolin Guo

  3. Edmond H. Fischer Signal Transduction Laboratory, College of Life Sciences, Jilin University, Changchun, 130023, People’s Republic of China

    Shu Xing & Xueqi Fu

  4. State Key Laboratory of Coordination Chemistry, Nanjing University, Nanjing, 210093, People’s Republic of China

    Miaoli Zhu

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  1. Liping Lu
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  2. Sulian Wang
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  3. Miaoli Zhu
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  4. Zhiwei Liu
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Correspondence to Miaoli Zhu, Maolin Guo or Xueqi Fu.

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Lu, L., Wang, S., Zhu, M. et al. Inhibition protein tyrosine phosphatases by an oxovanadium glutamate complex, Na2[VO(Glu)2(CH3OH)](Glu = glutamate). Biometals 23, 1139–1147 (2010). https://doi.org/10.1007/s10534-010-9363-8

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