X-ray absorption spectroscopy studies of the adducts formed between cytotoxic gold compounds and two major serum proteins
Tóm tắt
Gold metallodrugs form a class of promising antiproliferative agents showing a high propensity to react with proteins. We exploit here X-ray absorption spectroscopy (XAS) methods [both X-ray absorption near-edge spectroscopy (XANES) and extended X-ray absorption fine structure (EXAFS)] to gain insight into the nature of the adducts formed between three representative gold(I, III) metallodrugs (i.e., auranofin, [Au(2,2′-bipyridine)(OH)2](PF6), Aubipy, and dinuclear [Au2(6,6′-dimethyl-2,2′-bipyridine)2(μ-O)2](PF6)2, Auoxo6) and two major plasma proteins, namely, bovine serum albumin (BSA) and human serum apotransferrin (apoTf). The following metallodrug–protein systems were investigated in depth: auranofin/apoTf, Aubipy/BSA, and Auoxo6/apoTf. XANES spectra revealed that auranofin, upon protein binding, conserves its gold(I) oxidation state. Protein binding most probably takes place through release of the thiosugar ligand and its subsequent replacement by a thiol (or a thioether) from the protein. This hypothesis is independently supported by EXAFS results. In contrast, the reactions of Aubipy with serum albumin and of Auoxo6 with serum apoTf invariantly result in gold(III) to gold(I) reduction. Gold(III) reduction, clearly documented by XANES, is accompanied, in both cases, by release of the bipyridyl ligands; for Auoxo6 cleavage of the gold–gold dioxo bridge is also observed. Gold(III) reduction leads to formation of protein-bound gold(I) species, with deeply modified metal coordination environments, as evidenced by EXAFS. In these adducts, the gold(I) centers are probably anchored to the protein through nitrogen donors. In general, these two XAS methods, i.e., XANES and EXAFS, used here jointly, allowed us to gain independent structural information on metallodrug/protein systems; detailed insight into the gold oxidation state and the local environment of protein-bound metal atoms was achieved in the various cases.
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Espósito BP, Najjar R (2002) Coord Chem Rev 232:137
Liang X, Campopiano DJ, Sadler PJ (2007) Chem Soc Rev 36:968
Timerbaev AR, Hartinger CG, Aleksenko SS, Keppler BK (2006) Chem Rev 106:2224
Christodoulou J, Sadler PJ, Tucker A (1995) FEBS Lett 376:1
Patel SU, Sadler PJ, Tucker A, Viles JH (1993) J Am Chem Soc 115:9285
Nobili S, Mini E, Landini I, Gabbiani C, Casini A, Messori L (2010) Med Res Rev 30:550
Casini A, Kelter G, Gabbiani C, Cinellu MA, Minghetti G, Fregona D, Fiebig HH, Messori L (2009) J Biol Inorg Chem 14:1139
Ivanov AI, Christodoulou J, Parkinson JA, Barnham KJ, Tucker A, Woodrow J, Sadler PJ (1998) J Biol Chem 273:14721
Shaw CF III (1999) Chem Rev 99:2589
Marcon G, Messori L, Orioli P, Cinellu MA, Minghetti G (2003) Eur J Biochem 270:4655
Talib J, Beck JL, Ralph SF (2006) J Biol Inorg Chem 11:559
Boffi F, Ascone I, Della Longa S, Girasole M, Yalovega G, Soldatov A, Varoli-Piazza A, Congiu Castellano A (2003) Eur Biophys J 32:329
Ascone I, Strange R (2009) J Synchrotron Radiat 16:413
Michalke BJ (2010) Trace Elem Med Biol 24:69
Gabbiani C, Magherini F, Modesti A, Messori L (2010) AntiCancer Agents Med Chem 10:324
Levina A, Mitra A, Lay PA (2009) Metallomics 1:458
Finney L, Chishti Y, Khare T, Giometti C, Levina A, Lay PA, Vogt S (2010) ACS Chem Biol 5:577
Lobinski R, Moulin C, Ortega R (2006) Biochimie 88:1591
Ortega R, Devès G, Carmona A (2009) J R Soc Interface 5:S649
Ascone I, Messori L, Casini A, Gabbiani C, Balerna A, Dell’Unto F, Congiu Castellano A (2008) Inorg Chem 47:8629
Liu M, Lim ZJ, Gwee YY, Levina A, Lay PA (2010) Angew Chem Int Ed 49:1661
Hall MD, Foran GJ, Zhang M, Beale PJ, Hambley TW (2003) J Am Chem Soc 125:7524
Hall MD, Alderden RA, Zhang M, Beale PJ, Cai Z, Lai B, Stampfl APJ, Hambley TW (2006) J Struct Biol 155:38
Laib JE, Shaw CF 3rd, Petering DH, Eidsness MK, Elder RC, Garvey JS (1985) Biochemistry 24:1977
Coffer MT, Shaw CF III, Eidsness MK, Watkins JW II, Elder RC (1986) Inorg Chem 25:333
Elder RC, Eidsness MK (1987) Chem Rev 87:1027
Soldatov MA, Ascone I, Congiu-Castellano A, Messori L, Cinellu MA, Balerna A, Soldatov AV, Yalovega G (2009) J Phys Conf Ser 190:012210
Casini A, Cinellu MA, Minghetti G, Gabbiani C, Coronnello M, Mini E, Messori L (2006) J Med Chem 49:5524
Ciatto G, D’Acapito F, Boscherini F, Mobilio S (2004) J Synchrotron Radiat 11:278
Pascarelli S, D’Acapito F, Antonioli G, Balerna A, Boscherini F, Cimino R, Dalba G, Fornasini P, Licheri G, Meneghini C, Rocca F, Mobilio S (1995) ESRF Newsl 23:17
Lee PA, Citrin PH, Eisenberger P, Kincaid BM (1981) Rev Mod Phys 53:769
Hill DT, Sutton BM (1980) Cryst Struct Commun 9:679
Tong YY, Pombiero AJL, Hughes DL, Richards RL (1995) Transition Met Chem 20:372
Gabbiani C, Casini A, Messori L, Guerri A, Cinellu MA, Minghetti G, Corsini M, Rosani C, Zanello P, Arca M (2008) Inorg Chem 47:2368
Cinellu MA, Minghetti G, Pinna MV, Stoccoro S, Zucca A, Manassero M (2000) J Chem Soc Dalton Trans 1261
Marcon G, Carotti S, Coronnello M, Messori L, Mini E, Orioli P, Mazzei T, Cinellu MA, Minghetti G (2002) J Med Chem 45:1672
Lu ZH, Sham TK, Vos M, Bzowski A, Mitchell JV, Norton PR (1992) Phys Rev B 45:8811
Gardea-Torresdey JL, Tiemann KJ, Parson JG, Gamez G, Herrera I, Jose-Yacaman M (2002) Microchem J 71:193
Penner-Hahn JE (1999) Coord Chem Rev 190–192:1101
Penner-Hahn JE (2005) Coord Chem Rev 249:161
Levina A, Armstrong RS, Lay PA (2005) Coord Chem Rev 249:141
Ulery AL, Drees LR (eds) (2008) Methods of soil analysis—mineralogical methods. Soil Science Society of America Book Series No. 5. Madison, WI
Zou J, Taylor P, Dornan J, Robinson SP, Walkinshaw MD, Sadler PJ (2000) Angew Chem Int Ed 39:2931
Hill DT, Isab AA, Griswold DE, Di Martino MJ, Matz ED, Figueroa AL, Wawro JE, DeBrosse C, Reiff WM, Elder RC, Jones B, Webb JW, Shaw CF (2010) Inorg Chem 49:7663