Metalloproteomics as an interdisciplinary area involving proteins and metals

Expert Review of Proteomics

Volumn 7, Issue 3, 2010, Pages 387-400

  Da Silva, Marcelo AO ^a   Sussulini, Alessandra ^a   Arruda, Marco AZ ^a  

^a UNIVERSITY OF CAMPINAS   (Brazil)

Author keywords

2D PAGE; HPLC; Isotope dilution; Laser ablation; Mass spectrometry; Qualitative metalloproteomics; Quantitative metalloproteomics; Sample preparation; Separation

Indexed keywords

ISOTOPE; METAL;

CAPILLARY ELECTROPHORESIS; CYCLOTRON; DILUTION; GEL ELECTROPHORESIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; METALLOPROTEOMIC; POLYACRYLAMIDE GEL ELECTROPHORESIS; PROTEOMICS; REVIEW;

ANALYTIC SAMPLE PREPARATION METHODS; HUMANS; ISOTOPE LABELING; METALLOPROTEINS; METALS; PROTEOMICS; SPECTROPHOTOMETRY, ATOMIC;

EID: 77953588700     PISSN: 14789450     EISSN: 17448387     Source Type: Journal    
DOI: 10.1586/epr.10.16     Document Type: Review

References (111)

1. Gao YX, Chen CY, Chai ZF. Advanced nuclear analytical techniques for metalloproteomics. J. Anal. At. Spectrom. 22, 856-866 (2007).
2. Mounicou S, Szpunar J, Lobinski R. Metallomics: the concept and methodology. Chem. Soc. Rev. 38, 1119-1138 (2009).
3. Garcia JS, Magalhães CS, Arruda MAZ. Trends in metal-binding and metalloprotein analysis. Talanta 69, 1-15 (2006).
4. Lu Y, Yeung N, Sierack N, Marshall NM. Design of functional metalloproteins. Nature 460, 855-862 (2009).
5. Hay RW. Bio-inorganic Chemistry. Ellis Horwood Limited, John Wiley & Sons, Chichester, UK (1987).
6. Shi W, Chance MR. Metallomics and metalloproteomics, Cell. Mol. Life Sci. 65, 3040-3048 (2008).
7. Szpunar J. Metallomics: a new frontier in analytical chemistry. Anal. Bioanal. Chem. 378, 54-56 (2004).
8. Waldron KJ, Rutherford JC, Ford D, Robinson NJ. Metalloproteins and metal sensing. Nature 460, 823-830 (2009).
9. Irving H, Williams RJP. Order of stability of metal complexes. Nature 162, 746-747 (1948).
10. Meyer JA, Spence DM. A perspective on the role of metals in diabetes: past findings and possible future directions. Metallomics 1, 32-41 (2009).
11. Kodama H, Fujisawa C. Copper metabolism and inherited copper transport disorders: molecular mechanisms, screening, and treatment. Metallomics 1, 42-52 (2009).
12. Fatemi N, Sarkar B. Insights into the mechanism of copper transport by the Wilson and Menkes disease coppertransport ATPases. Inorg. Chim. Acta 339, 179-187 (2002).
13. His G, Cox DW. A comparison of the mutation spectra of Menkes disease and Wilson disease. Hum. Genet. 114, 165-172 (2004).
14. Arruda MAZ, Azevedo RA. Metallomics and chemical speciation: towards a better understanding of metal-induced stress in plants. Ann. Appl. Biol. 155, 301-307 (2009).
15. Cottingham K. Systems biology: a boon for analytical chemists? Anal. Chem. 77, 197A-200A (2005).
16. Hood L, Heath JR, Phelps ME, Lin B. Systems biology and new technologies enable predictive and preventative medicine. Science 306, 640-643 (2004).
17. Nicholson JK, Lindon JC. Systems biology: metabonomics. Nature 455, 1054-1056 (2008).
18. Arruda MAZ. Trends in Sample Preparation. Nova Science, NY, USA (2007).
19. Sevcenco AM, Pinkse MWH, Bol E et al. The tungsten metallome of Pyrococcus furiosus. Metallomics 1, 395-402 (2009).
20. Chevreux S, Roudeau S, Fraysse A et al. Multimodal analysis of metals in copperzinc superoxide dismutase isoforms separated on electrophoresis gels. Biochimie 91, 1324-1327 (2009).
21. Berrada W, Naya A, Iddar A, Bourhim N. Purification and characterization of cytosolic glycerol-3-phosphate dehydrogenase from skeletal muscle of jerboa ( Jaculus orientalis) Mol. Cell. Biochem. 231, 117-127 (2002).
22. Chen SX, Shao ZZ, Isolation and diversity analysis of arsenite-resistant bacteria in communities enriched from deep-sea sediments of the Southwest Indian Ocean Ridge. Extremophiles 13, 39-48 (2009).
23. Raab A, Ploselli B, Munro C, Thomas- Oates J, Feldmann J. Evaluation of gel electrophoresis conditions for the separation of metal-tagged proteins with subsequent laser ablation ICP-MS detection. Electrophoresis 30, 303-314 (2009).
24. Pecsvaradi A, Nagy Z, Varga A et al. Chloroplastic glutamine synthetase is activated by direct binding of aluminium. Physiol. Plant 135, 43-50 (2009).
25. Sussulini A, Garcia JS, Mesko MF et al. Evaluation of soybean seed protein extraction focusing on metalloprotein analysis. Microchim. Acta 158, 173-180 (2006).
26. Magalhães CS, Arruda MAZ. Sample preparation for metalloprotein analysis: a case of study using horse chestnuts. Talanta 71, 1958-1963 (2007).
27. Kingston HM, Haswell SJ. Microwave- Enhanced Chemistry. Fundamentals, Sample Preparation and Applications. ACS, Washington DC, USA (1997).
28. García Salgado S, Quijano Nieto MA, Bonilla Simón MM. Determination of soluble toxic arsenic species in alga samples by microwave-assisted extraction and high performance liquid chromatographyhydride generation-inductively coupled plasma-atomic emission spectrometry. J. Chromatrogr. A 1129, 54-60 (2006).
29. Morales-Muñoz S, Luque-Garcia JL, Castro MLD. Pure and modified water assisted by auxiliary energies: an environmental friendly extractant for sample preparation. Anal. Chim. Acta 557, 278-286 (2006).
30. Verbi FM, Arruda SCC, Rodriguez APM, Pérez CA, Arruda MAZ. Metal-binding proteins scanning and determination by combining gel electrophoresis, synchrotron radiation x-ray fluorescence and atomic spectrometry. J. Biochem. Biophys. Meth. 62, 97-109 (2005).
31. Sussulini A, Souza GHMF, Eberlin MN, Arruda MAZ. Comparative metallomics for transgenic and non-transgenic soybeans. J. Anal. At. Spectrom. 22, 1501-1506 (2007).
32. Sussulini A, Garcia JS, Arruda MAZ. Microwave-assisted decomposition of polyacrylamide gels containing metalloproteins using mini-vials: an auxiliary strategy for metallomics studies. Anal. Biochem. 361, 146-148 (2007).
33. Neverova I, Eyk JEV. Role of chromatographic technique in proteomic analysis. J. Chromatogr. B 815, 51-63 (2005).
34. Manley SA, Byrns S, Lyon AW, Brown P, Gailer J. Simultaneous Cu-, Fe-, and Zn-specific detection of metalloproteins contained in rabbit plasma by size-exclusion chromatography-inductively coupled plasma atomic emission spectroscopy. J. Biol. Inorg. Chem. 14, 61-74 (2009).
35. Manley SA, Gailer J. Analysis of the plasma proteome by SEC-ICP-AES: bridging proteomics and metabolomics. Expert Rev. Proteomics 6(3), 251-265 (2009).
36. Pioselli B, Munro C, Raab A et al. Denaturing and non-denaturing microsolution isoelectric focusing to mine the metalloproteome. Metallomics 1, 501-510 (2009).
37. Arias-Borrego A, Garcia-Barrera T, Gómez-Ariza L. Speciation of manganese binding to biomolecules in pine nuts (Pinus pinea) by two-dimensional liquid chromatography coupled to ultraviolet and inductively coupled plasma mass spectrometry detectors followed by identification by electrospray ionization mass spectrometry. Rapid Commun. Mass Spectrom. 22, 3053-3060 (2008).
38. Rodrígues-Fariñas N, Gomez-Gomez MM, Camara Rica C. Study of tungstate-protein interaction in human serum by LC-ICPMS and MALDI-TOF. Anal. Bioanal. Chem. 390, 29-35 (2008).
39. Giusti P, Schaumlöffel D, Preud'Homme H, Szpunar J, Lobinski R. Selenopeptide mapping in a selenium-yeast protein digest by parallel nanoHPLC-ICP-MS and nanoHPLC-electrospray-MS/MS after on-line preconcentration. J. Anal. At. Spectrom. 21, 26-32 (2006).
40. Muñiz CS, Gayón JMM, Alonso IG, Sanz-Medel A. Speciation of essential elements in human serum using anionexchange chromatography coupled to post-column isotope dilution analysis with double focusing ICP-MS. J. Anal. At. Spectrom. 16, 587-592 (2001).
41. Sanz-Medel, A, Montes-Bayón, M, Sánchez MLF. Trace element speciation by ICP-MS in large biomolecules and its potential for proteomics. Anal. Bioanal. Chem. 377, 236-247 (2003).
42. Xu M, Yang L, Wang Q. Quantification of selenium-tagged proteins in human plasma using species-unspecific isotope dilution ICP-DRC-qMS coupled online with anion exchange chromatography. J. Anal. At. Spectrom. 23, 1545-1549 (2008).
43. Motoyama A, Yates III JR, Multidimensional LC separations in shotgun proteomics. Anal Chem. 80, 7187-7193 (2008).
44. González-Fernández M, García-Barrera T, Arias-Borrego A et al. Metallomics integrated with proteomics in deciphering metal-related environmental issues. Biochimie 91, 1311-1317 (2009).
45. Cañas B, Piñero C, Calvo E, López-Ferrer D, Gallardo JM. Trends in sample preparation for classical and second generation proteomics. J. Chromatogr. A 1153, 235-258 (2007).
46. Isaaq HJ, Chan KC, Janini GM, Conrads TP, Veenstra TD. Multidimensional separation of peptides for effective proteomic analysis. J. Chromatogr. B 817, 35-47 (2005).
47. Chong FC, Tan WS, Biak DRA, Ling TC, Tey BT. Purification of histidine-tagged nucleocapsid protein of Nipah virus using immobilized metal affinity chromatography. J. Chromatogr. B. 877, 1561-1567 (2009).
48. Kung CS, Huang W, Huang Y, Yeh K. Proteomic survey of copper-binding proteins in Arabidopsis roots by immobilized metal affinity chromatography and mass spectrometry. Proteomics 6, 2746-2758 (2006).
49. Roelofsen H, Balgobind R, Vonk RJ. Proteomic analysis of copper metabolism in an in vitro model of Wilson disease using surface enhanced laser desorption/ ionization-time of flight-mass spectrometry. J. Cell Mol. Biochem. 93, 732-740 (2004).
50. Smith SD, She Y, Roberts EA, Sarkar B. Using immobilized metal affinity chromatography, two-dimensional electrophoresis and mass spectrometry to identify hepatocellular proteins with copper-binding ability. J. Proteom. Res. 3, 834-840 (2004).
51. Ribeiro MB, Vijayalakshmi M. Todorova-Balvay D, Bueno SMA. Effect of IDA and TREM chelating agents and buffer systems on the purification of human IgG with immobilized nickel affinity membranes. J. Chromatogr. B 861, 64-73 (2008).
52. Hidalgo A, Betancor L, Mateo C et al. Purification of a catalase from Thermus thermophilus via IMAC chromatography: effect of the support. Biotechnol. Prog. 20, 1578-1582 (2004).
53. Watanabe S, Nagano S, Duce J et al. Increased affinity for copper mediated by cysteine 111 in forms of mutant superoxide dismutase 1 linked to amyotrophic lateral sclerosis. Free Radical Biol. Med. 42, 1534-1542 (2007).
54. Tsai C, Wang Y, Chen Y et al. Immobilized metal affinity chromatography revisited: pH/acid control toward high selectivity in phosphoproteomics. J. Proteom. Res. 7, 4058-4069 (2008).
55. Paradela A, Albar JP. Advances in analysis of protein phosphorilation. J. Proteom. Res. 7, 1809-1818 (2008).
56. Haselberg R, Jong GJ, Somsen GW. Capillary electrophoresis-mass spectrometry for the analysis of intact proteins. J. Chromatogr. A 1159, 81-109 (2007).
57. Prange A, Pröfrock D. Application of CE-ICP-MS and CE-ESI-MS in metalloproteomics: challenges, developments, and limitations. Anal. Bioanal. Chem. 383, 372-389 (2005).
58. Mounicou S, Lobinski R. Challenges to metallomics and analytical chemistry solutions. Pure Appl. Chem. 80, 2565-2575 (2008).
59. Polec-Pawlak K, Schaumlöffel D, Szpunar J, Prange A, Lobinski R. Analysis for metal complexes with metallothionein in rat liver by capillary zone electrophoresis using ICP double-focusing sector-field isotope dilution MS and electrospray MS detection. J. Anal. At. Spectrom. 17, 908-912 (2002).
60. Heegaard NHH, He X, Blomberg LG. Binding of Ca2+, Mg2+, and heparin by human serum amyloid P component in affinity capillary electrophoresis. Electrophoresis 27, 2609-2615 (2006).
61. Huhn C, Ramautar R, Wuhrer M, Somsen GW. Relevance and use of capillary coatings in capillary electrophoresis-mass spectrometry. Anal. Bioanal. Chem. 396, 297-314 (2010).
62. Álvarez-Llamas G, Campa MRF, Sanz-Medel A, Sample stacking capillary electrophoresis with ICP-(Q)MS detection for Cd, Cu and Zn speciation in fish liver metallothioneins. J. Anal. At. Spectrom. 18, 460-466 (2003).
63. Monton MRN, Terabe S. Sample enrichment techniques in capillary electrophoresis: focus on peptides and proteins. J. Chromatogr. B 841, 88-95 (2006).
64. Schaumlöffel D. Capillary liquid separation techniques with ICP MS detection. Anal. Bioanal. Chem. 379, 351-354 (2004).
65. Timerbaev AR, Aleksenko SS, Polec-Pawlak K et al. Platinum metallodrug-protein binding studies by capillary electrophoresis-inductively coupled plasma-mass spectrometry: characterization of interactions between Pt(II) complexes and human serum albumin. Electrophoresis 25, 1988-1995 (2004).
66. Polec-Pawlak K, Abramski JK, Semenova O et al. Platinum group metallodrug-protein binding studies by capillary electrophoresis - inductively coupled plasma-mass spectrometry: a further insight into the reactivity of a novel antitumor ruthenium(III) complex toward human serum proteins. Electrophoresis 27, 1128-1135 (2006).
67. Lierde VV, Chéry CC, Strijckmans K et al. Capillary electrophoresis hyphenated to inductively coupled plasma-sector field-mass spectrometry for the stoichiometric determination of Zn bound to Aeromonas hydrophila Zn b-lactamase. J. Anal. At. Spectrom. 19, 888-893 (2004).
68. Timerbaev AR, Keppler BK. Capillary electrophoresis of metal-based drugs. Anal. Biochem. 369, 1-7 (2007).
69. Hartinger CG, Keppler BK. CE in anticancer metallodrug research - an update. Electrophoresis 28, 3436-3446 (2007).
70. Sun X, Tsang C, Sun H. Identification and characterization of metallodrug binding proteins by (metallo)proteomics. Metallomics 1, 25-31 (2009).
71. Cooks RG, Ouyang Z, Takats Z, Wiseman JM. Ambient mass spectrometry. Science 311, 1556-1570 (2006).
72. Liu Y, Pan Y. Application of FT-ICR MS for the study of protein complexes. Appl. Spectrosc. Rev. 44, 231-244 (2009).
73. Tolmachev AV, Robinson EW, Wu S, Paša-Tolic L, Smith RD. FT-ICR MS optimization for the analysis of intact proteins. Int. J. Mass Spectrom. 287, 32-38 (2009).
74. Jänis J, Pasanen S, Rouvinen J, Vainiotalo P. Characterization of the pH-dependent dissociation of a multimeric metalloprotein Streptomyces rubiginosus xylose isomerase by ESI FT-ICR mass spectrometry. J. Mass Spectrom. 43, 1376-1380 (2008).
75. Becker JS, Zoriy M, Pickhardt C, Przybylski M, Becker JS. Investigation of Cu-, Zn- and Fe-containing human brain proteins using isotopic-enriched tracers by LA-ICP-MS and MALDI-FT-ICR-MS. Int. J. Mass Spectrom. 242, 135-144 (2005).
76. Becker JS, Zoriy M, Becker JS et al. Determination of phosphorous-, copper-, and zinc-containing human brain proteins by LA-ICPMS and MALDI-FTICR-MS. Anal. Chem. 77, 5851-5860 (2005).
77. Kanu AB, Dwivedi P, Tam M, Matz L, Hill HH Jr. Ion mobility-mass spectrometry. J. Mass Spectrom. 43, 1-22 (2008).
78. Carazzone C, Raml R, Pergantis SA. Nanoelectrospray ion mobility spectrometry online with inductively coupled plasma-mass spectrometry for sizing large proteins, DNA, and nanoparticles. Anal. Chem. 80, 5812-5818 (2008).
79. Lobinski R, Schaumlöffel D, Szpunar J. Mass spectrometry in bioinorganic analytical chemistry. Mass Spectrom. Rev. 25, 255-289 (2006).
80. Beauchemin D. Inductively coupled plasma mass spectrometry. Anal. Chem. 76, 3395-3416 (2004).
81. Wang M, Feng WY, Zhao YL, Chai ZF. ICP-MS-based strategies for protein quantification. Mass Spectrom. Rev. 29(2), 326-348 (2010).
82. Sanz-Medel A, Montes-Bayón M, de la Campa MRF, Encinar JR, Bettmer J. Elemental mass spectrometry for quantitative proteomics. Anal. Bioanal. Chem. 390, 3-16 (2008).
83. Becker JS, Jakubowski N. The synergy of elemental and biomolecular mass spectrometry: new analytical strategies in life sciences. Chem. Soc. Rev. 38, 1969-1983 (2009).
84. Persson DP, Hansen TH, Laursen KH, Schjoerring JK, Husted S. Simultaneous iron, zinc, sulfur and phosphorous speciation analysis of barley grain tissues using SEC-ICP-MS and IP-ICP-MS. Metallomics 1, 418-426 (2009).
85. Barbosa Jr F, Gerlach RF, Tanus-Santos JE. Matrix metalloproteinase-9 activity in plasma correlates with plasma and whole blood lead concentrations. Basic Clin. Pharmacol. Toxicol. 98, 559-564 (2006).
86. Pomazal K, Prohaska C, Steffan I. Hydrophobic interaction chromatographic separation of proteins in human blood fractions hyphenated to atomic spectrometry as detector of essential elements. J. Chromatogr. A. 960, 143-150 (2002).
87. Ortega R. Synchrotron radiation for direct analysis of metalloproteins on electrophoresis gels. Metallomics 1, 137-141 (2009).
88. Silva MP, Tomal A, Pérez CA, Ribeiro- Silva A, Poletti ME. Determination of Ca, Fe, Cu and Zn and their correlations in breast cancer and normal adjacent tissues. X-ray Spectrom. 38, 103-111 (2009).
89. Becker JS, Lobinski R, Becker JS. Metal-imaging in non-denaturing 2D electrophoresis gels by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) for the detection of metalloproteins. Metallomics 1, 312-316 (2009).
90. Tastet L, Schaumlöffel D, Lobinski R. ICP-MS-assisted proteomics approach to the identification of selenium-containing proteins in selenium-rich yeast. J. Anal. At. Spectrom. 23, 309-317 (2008).
91. Becker JS, Zoriy M, Dressler VL, Wu B, Becker JS. Imaging of metals and metal-containing species in biological tissues and on gels by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS): a new analytical strategy for applications in life sciences. Pure Appl. Chem. 80, 2643-2655 (2008).
92. Becker JS, Boulyga SF, Pickhardt C, Becker J, Buddrus S, Przybylski M. Determination of phosphorus in small amounts of protein samples by ICP-MS. Anal. Bioanal. Chem. 375, 561-566 (2003).
93. Becker JS. Inorganic Mass Spectrometry Principles and Applications. John Wiley & Sons, Chichester, UK (2007).
94. Neuhoff V, Arold N, Taube D, Ehrhardt W. Improved staining of proteins in polyacrylamide gels including isoelectric focusing gels with clear background at nanogram sensitivity using Coomassie Brilliant Blue G-250 and R-250. Electrophoresis 9, 255-262 (1988).
95. Shevchenko A, Wilm M, Vorm O, Mann M. Mass spectrometric sequencing of proteins silver-stained polyacrylamide gels. Anal. Chem. 68, 850-858 (1996).
96. Marshall P, Heudi O, Bains S, Freeman NH, Abou-Shakra F, Reardon K. The determination of protein phosphorylation on electrophoresis gel blots by laser ablation inductively coupled plasma-mass spectrometry. Analyst 127, 459-461 (2002).
97. Kindness A, Sekaran CN, Feldmann J. Two-dimensional mapping of copper and zinc in liver sections by laser ablation - inductively coupled plasma mass spectrometry. Clin. Chem. 49, 1916-1923 (2003).
98. Wind M, Feldmann I, Jakubowski N, Lehmann WD. Spotting and quantification of phosphoproteins purified by gel electrophoresis and laser ablation-element mass spectrometry with phosphorus-31 detection. Electrophoresis 24, 1276-1280 (2003).
99. Brüchert W, Bettmer J. Online coupling of gel electrophoresis and inductively coupled plasma-sector field-mass spectrometry for the determination of dsDNA fragments. Anal. Chem. 77, 5072-5075 (2005).
100. Elliott VL, McLeod CW, Marshall PS. Combination of gel electrophoresis and ICP-mass spectrometry - novel strategies for phosphoprotein measurement. Anal. Bioanal. Chem. 383, 416-423 (2005).
101. Jiménez MS, Gomez MT, Rodriguez L, Martinez L, Castillo JR. Some pitfalls in PAGE-LA-ICP-MS for quantitative elemental speciation of dissolved organic matter and metallomics. Anal. Bioanal. Chem. 393, 699-707 (2009).
102. Becker JS, Mounicou S, Zoriy M, Becker JS, Lobinski R. Analysis of metal-binding proteins separated by non-denaturating gel electrophoresis using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). Talanta 76, 1183-1188 (2008).
103. Wind M, Wegener A, Eisenmenger A, Kellner R, Lehmann WD. Sulfur as the key element for quantitative protein analysis by capillary liquid chromatography coupled to element mass spectrometry. Angew. Chem. Int. Ed. 42, 3425-3427 (2003). (Pubitemid 36975342)
104. Meija J, Mester Z. Paradigms in isotope dilution mass spectrometry for elemental speciation analysis. Anal. Chim. Acta 607, 115-125 (2008).
105. Vogl J. Characterisation of reference materials by isotope dilution mass spectrometry. J. Anal. At. Spectrom. 22, 475-492 (2007).
106. Ammann AA. Inductively coupled plasma mass spectrometry (ICP-MS): a versatile tool. J. Mass Spectrom. 42, 419-427 (2007).
107. Rottmann L, Heumann KG. Development of an online isotope-dilution technique with HPLC ICP-MS for the accurate determination of elemental species. Fres. J. Anal. Chem. 350, 221-227 (1994).
108. Monperrus M, Krupp E, Amouroux D, Donard OFX, Martín-Doimeadios RCR. Potential and limits of speciated isotopedilution analysis for metrology and assessing. Trends Anal. Chem. 23, 261-272 (2004).
109. Busto MEC, Montes-Bayón M, Bettmer J, Sanz-Medel A. Stable isotope labelling and FPLC-ICP-SFMS for the accurate determination of clinical iron status parameters in human serum. Analyst 133, 379-384 (2008).
110. Harrington CF, Vidler DS, Watts MJ, Hall JF. Potential for using isotopically altered metalloproteins in species-specific isotope dilution analysis of proteins by HPLC coupled to inductively coupled plasma mass spectrometry. Anal. Chem. 77, 4034-4041 (2005).
111. Sarmiento-González A, Encinar JR, Cantarero-Roldán AM, Marchante- Gayón JM, Sanz-Medel A. HPLC-ICPMS and stable isotope labeled approaches to assess quantitatively Ti(IV) uptake by transferrin in human blood serum. Anal. Chem. 80, 8702-8711 (2008).