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Probing the Protein: Ion Mobility Spectrometry

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Gold(I,III) Complexes Designed for Selective Targeting and Inhibition of Zinc Finger Proteins

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Abstract

Auration of zinc finger peptides represents a topic of wide interest in bioinorganic chemistry as well as a fundamental problem for inorganic chemistry, since we are evaluating the replacement of a tetrahedrally-coordinated Zn(II) by a linear-coordinated Au(I). The compound [AuCl(Et3P)] (I-1) was selected as Au(I) donor, and the interaction with NCp7 (ZnF2) and Sp1 (F3) were studied by traveling-wave ion mobility mass spectrometry (TWIM-MS) coupled with collision induced dissociation (CID). This approach allowed inequivocal elucidation of specific binding sites and modes of gold-modified NCp7 (ZnF2) and Sp1 (ZnF3). While linear Cys-Au-Cys is indicated for NCp7 (ZnF2), a Cys-Au-His mode is indicated for the Sp1 (ZnF3) case.

Parts of this chapter has been reproduced with permission from Wiley. https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.201612494.

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References

  1. Hartinger, C.G., Groessl, M., Meier, S.M., Casini, A., Dyson, P.J., Tavernelli, I., Keppler, B.K., Jaehde, U., Messori, L., Messori, L., et al.: Application of mass spectrometric techniques to delineate the modes-of-action of anticancer metallodrugs. Chem. Soc. Rev. 42(14), 6186 (2013). https://doi.org/10.1039/c3cs35532b

    Article  CAS  PubMed  Google Scholar 

  2. Quintal, S.M., dePaula, Q.A., Farrell, N.P.: Zinc finger proteins as templates for metal ion exchange and ligand reactivity. Chemical and biological consequences. Metallomics 3(2), 121–139 (2011). https://doi.org/10.1039/c0mt00070a

    Article  CAS  PubMed  Google Scholar 

  3. Spell, S.R., Farrell, N.P.: Synthesis and properties of the first [Au(dien)(N-heterocycle)]3+ compounds. Inorg. Chem. 53(1), 30–32 (2014). https://doi.org/10.1021/ic402772j

    Article  CAS  PubMed  Google Scholar 

  4. Laskay, Ü.A., Garino, C., Tsybin, Y.O., Salassa, L., Casini, A., Laskay, U.A., Garino, C., Tsybin, Y.O., Salassa, L., Casini, A.: Gold finger formation studied by high-resolution mass spectrometry and in silico methods. Chem. Commun. 51(9), 1612–1615 (2015). https://doi.org/10.1039/C4CC07490D

    Article  CAS  Google Scholar 

  5. Spell, S.R., Mangrum, J.B., Peterson, E.J., Fabris, D., Ptak, R., Farrell, N.P.: Au(III) compounds as HIV nucleocapsid protein (NCp7)–nucleic acid antagonists. Chem. Commun. 53(1), 91–94 (2017). https://doi.org/10.1039/C6CC07970A

    Article  CAS  Google Scholar 

  6. Karver, M.R., Krishnamurthy, D., Kulkarni, R.A., Bottini, N., Barrios, A.M.: Identifying potent, selective protein tyrosine phosphatase inhibitors from a library of Au(I) complexes. J. Med. Chem. 52(21), 6912–6918 (2009). https://doi.org/10.1021/jm901220m

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Diakun, G.P., Fairall, L., Klug, A.: EXAFS study of the zinc-binding sites in the protein transcription factor IIIA. Nature 324(6098), 698–699 (1986). https://doi.org/10.1038/324698a0

    Article  CAS  PubMed  Google Scholar 

  8. Berners-Price, S.J., Filipovska, A.: Gold compounds as therapeutic agents for human diseases. Metallomics 3(9), 863 (2011). https://doi.org/10.1039/c1mt00062d

    Article  CAS  PubMed  Google Scholar 

  9. Bindoli, A., Rigobello, M.P., Scutari, G., Gabbiani, C., Casini, A., Messori, L.: Thioredoxin reductase: a target for gold compounds acting as potential anticancer drugs. Coord. Chem. Rev. 253(11), 1692–1707 (2009). https://doi.org/10.1016/j.ccr.2009.02.026

    Article  CAS  Google Scholar 

  10. Nobili, S., Mini, E., Landini, I., Gabbiani, C., Casini, A., Messori, L.: Gold compounds as anticancer agents: chemistry, cellular pharmacology, and preclinical studies. Med. Res. Rev. 30(3), 550–580 (2009). https://doi.org/10.1002/med.20168

    Article  CAS  Google Scholar 

  11. Ott, I.: On the medicinal chemistry of gold complexes as anticancer drugs. Coord. Chem. Rev. 253(11), 1670–1681 (2009). https://doi.org/10.1016/j.ccr.2009.02.019

    Article  CAS  Google Scholar 

  12. Serebryanskaya, T.V., Lyakhov, A.S., Ivashkevich, L.S., Schur, J., Frias, C., Prokop, A., Ott, I., Rubbiani, R., Wahrig, B., Ott, I., et al.: Gold(I) thiotetrazolates as thioredoxin reductase inhibitors and antiproliferative agents. Dalton Trans. 44(3), 1161–1169 (2015). https://doi.org/10.1039/C4DT03105A

    Article  CAS  PubMed  Google Scholar 

  13. Larabee, J.L., Hocker, J.R., Hanas, J.S.: Mechanisms of aurothiomalate-Cys2His2 zinc finger interactions. Chem. Res. Toxicol. 18(12), 1943–1954 (2005). https://doi.org/10.1021/tx0501435

    Article  CAS  PubMed  Google Scholar 

  14. Handel, M.L., DeFazio, A., Watts, C.K., Day, R.O., Sutherland, R.L.: Inhibition of DNA binding and transcriptional activity of a nuclear receptor transcription factor by aurothiomalate and other metal ions. Mol. Pharmacol. 40(5), 613–618 (1991)

    CAS  PubMed  Google Scholar 

  15. Chertova, E.N., Kane, B.P., McGrath, C., Johnson, D.G., Sowder, R.C., Arthur, L.O., Henderson, L.E.: Probing the topography of HIV-1 nucleocapsid protein with the alkylating agent N-ethylmaleimide. Biochemistry 37(51), 17890–17897 (1998). https://doi.org/10.1021/bi980907y

    Article  CAS  PubMed  Google Scholar 

  16. Sechi, S., Chait, B.T.: Modification of cysteine residues by alkylation. A tool in peptide mapping and protein identification. Anal. Chem. 70(24), 5150–5158 (1998). https://doi.org/10.1021/ac9806005

    Article  CAS  PubMed  Google Scholar 

  17. Mendoza, V.L., Vachet, R.W.: Probing protein structure by amino acid-specific covalent labeling and mass spectrometry. Mass Spectrom. Rev. 28(5), 785–815 (2009). https://doi.org/10.1002/mas.20203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Shaw, C.F.: Gold-based therapeutic agents. Chem. Rev. 99(9), 2589–2600 (1999). https://doi.org/10.1021/cr980431o

    Article  CAS  Google Scholar 

  19. Abbehausen, C., Peterson, E.J., De Paiva, R.E.F., Corbi, P.P., Formiga, A.L.B., Qu, Y., Farrell, N.P.: Gold(I)-phosphine-N-heterocycles: biological activity and specific (ligand) interactions on the C-terminal HIVNCp7 zinc finger. Inorg. Chem. 52(19), 11280–11287 (2013). https://doi.org/10.1021/ic401535s

    Article  CAS  PubMed  Google Scholar 

  20. Hu, W., Luo, Q., Wu, K., Li, X., Wang, F., Chen, Y., Ma, X., Wang, J., Liu, J., Xiong, S., et al.: The anticancer drug cisplatin can cross-link the interdomain zinc site on human albumin. Chem. Commun. 47(21), 6006 (2011). https://doi.org/10.1039/c1cc11627d

    Article  CAS  Google Scholar 

  21. Maynard, A.T., Huang, M., Rice, W.G., Covell, D.G.: Reactivity of the HIV-1 nucleocapsid protein p7 zinc finger domains from the perspective of density-functional theory. Proc. Natl. Acad. Sci. U. S. A. 95(20), 11578–11583 (1998). https://doi.org/10.1073/pnas.95.20.11578

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Maynard, A.T., Covell, D.G.: Reactivity of zinc finger cores:? Analysis of protein packing and electrostatic screening. J. Am. Chem. Soc. 123(6), 1047–1058 (2001). https://doi.org/10.1021/ja0011616

    Article  CAS  PubMed  Google Scholar 

  23. Morcock, D.R., Thomas, J.A., Gagliardi, T.D., Gorelick, R.J., Roser, J.D., Chertova, E.N., Bess, J.W., Ott, D.E., Sattentau, Q.J., Frank, I., et al.: Elimination of retroviral infectivity by N-ethylmaleimide with preservation of functional envelope glycoproteins. J. Virol. 79(3), 1533–1542 (2005). https://doi.org/10.1128/JVI.79.3.1533-1542.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Levin, J.G., Guo, J., Rouzina, I., Musier-Forsyth, K., Rouzina, I., Musier-Forsyth, K.: Nucleic acid chaperone activity of HIV-1 nucleocapsid protein: critical role in reverse transcription and molecular mechanism. Prog. Nucleic Acid Res. Mol. Biol. 80(05), 217–286 (2005). https://doi.org/10.1016/S0079-6603(05)80006-6

    Article  PubMed  Google Scholar 

  25. Mori, M., Kovalenko, L., Lyonnais, S., Antaki, D., Torbett, B.E., Botta, M., Mirambeau, G., Mély, Y.: Nucleocapsid protein: a desirable target for future therapies against HIV-1. Curr. Top. Microbiol. Immunol. 389, 53–92 (2015). https://doi.org/10.1007/82_2015_433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Garg, D., Torbett, B.E.: Advances in targeting nucleocapsid–nucleic acid interactions in HIV-1 therapy. Virus Res. 193, 135–143 (2014). https://doi.org/10.1016/j.virusres.2014.07.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Lee, J., Jayathilaka, L.P., Gupta, S., Huang, J.-S., Lee, B.-S.: Gold ion-angiotensin peptide interaction by mass spectrometry. J. Am. Soc. Mass Spectrom. 23(5), 942–951 (2012). https://doi.org/10.1007/s13361-011-0328-0

    Article  CAS  PubMed  Google Scholar 

  28. Zou, J., Taylor, P., Dornan, J., Robinson, S., Walkinshaw, M., Sadler, P.: First crystal structure of a medicinally relevant gold protein complex: unexpected binding of [Au(PEt3)]+ to histidine. Angew. Chemie 39(16), 2931–2934 (2000). https://doi.org/10.1002/1521-3773(20000818)39:16%3c2931:AID-ANIE2931%3e3.0.CO;2-W

    Article  CAS  Google Scholar 

  29. Franzman, M.A., Barrios, A.M.: Spectroscopic evidence for the formation of goldfingers. Inorg. Chem. 47(10), 3928–3930 (2008). https://doi.org/10.1021/ic800157t

    Article  CAS  PubMed  Google Scholar 

  30. Jacques, A., Lebrun, C., Casini, A., Kieffer, I., Proux, O., Latour, J.-M., Sénèque, O.: Reactivity of Cys 4 zinc finger domains with gold(III) complexes: insights into the formation of “gold fingers”. Inorg. Chem. 54(8), 4104–4113 (2015). https://doi.org/10.1021/acs.inorgchem.5b00360

    Article  CAS  PubMed  Google Scholar 

  31. Williams, J.P., Phillips, H.I.A., Campuzano, I., Sadler, P.J.: Shape changes induced by N-terminal platination of ubiquitin by cisplatin. J. Am. Soc. Mass Spectrom. 21(7), 1097–1106 (2010). https://doi.org/10.1016/j.jasms.2010.02.012

    Article  CAS  PubMed  Google Scholar 

  32. Williams, J.P., Brown, J.M., Campuzano, I., Sadler, P.J., Sadler, P.J., Clausen, H., Johnsen, A.H., Zubarev, R.A., Dawson, A., Aird, R.E., et al.: Identifying drug metallation sites on peptides using electron transfer dissociation (ETD), collision induced dissociation (CID) and ion mobility-mass spectrometry (IM-MS). Chem. Commun. 46(30), 5458 (2010). https://doi.org/10.1039/c0cc00358a

    Article  CAS  Google Scholar 

  33. Murray, B.S., Menin, L., Scopelliti, R., Dyson, P.J.: Conformational control of anticancer activity: the application of arene-linked dinuclear ruthenium(II) organometallics. Chem. Sci. 5(6), 2536 (2014). https://doi.org/10.1039/c4sc00116h

    Article  CAS  Google Scholar 

  34. Jurneczko, E., Cruickshank, F., Porrini, M., Clarke, D.J., Campuzano, I.D.G., Morris, M., Nikolova, P.V., Barran, P.E.: Probing the conformational diversity of cancer-associated mutations in p53 with ion-mobility mass spectrometry. Angew. Chemie Int. Ed. 52(16), 4370–4374 (2013). https://doi.org/10.1002/anie.201210015

    Article  CAS  Google Scholar 

  35. Choi, D., Alshahrani, A.A., Vytla, Y., Deeconda, M., Serna, V.J., Saenz, R.F., Angel, L.A.: Redox activity and multiple copper(I) coordination of 2His-2Cys oligopeptide. J. Mass Spectrom. 50(2), 316–325 (2015). https://doi.org/10.1002/jms.3530

    Article  CAS  PubMed  Google Scholar 

  36. Papayannopoulos, I.A.: The interpretation of collision-induced dissociation tandem mass spectra of peptides. Mass Spectrom. Rev. 14(1), 49–73 (1995). https://doi.org/10.1002/mas.1280140104

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Institute of Chemistry, University of Campinas, Campinas, Brazil

    Raphael Enoque Ferraz de Paiva

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  1. Raphael Enoque Ferraz de Paiva
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Correspondence to Raphael Enoque Ferraz de Paiva .

Appendix

Appendix

1.1 MS/MS Fragment Lists

See Tables 2.1, 2.2 and 2.3.

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Ferraz de Paiva, R.E. (2018). Probing the Protein: Ion Mobility Spectrometry. In: Gold(I,III) Complexes Designed for Selective Targeting and Inhibition of Zinc Finger Proteins. Springer Theses. Springer, Cham. https://doi.org/10.1007/978-3-030-00853-6_2

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