Analytical and Bioanalytical Chemistry

, Volume 402, Issue 3, pp 1041–1056

Zirconium arsenate-modified silica nanoparticles for specific capture of phosphopeptides and direct analysis by matrix-assisted laser desorption/ionization mass spectrometry

  • Pei-Xuan Zhao
  • Xiao-Feng Guo
  • Hong Wang
  • Chu-Bo Qi
  • He-Shun Xia
  • Hua-Shan Zhang
Original Paper


In this paper, we report, as far as we are aware, the first use of zirconium arsenate-modified silica nanoparticles (ZrAs-SNPs) for specific capture of phosphopeptides, followed by matrix-assisted laser desorption/ionization mass spectrometric (MALDI MS) analysis. Under the optimized enrichment conditions, the efficiency and specificity of ZrAs-SNPs were evaluated with tryptic digests of four standard proteins (α-casein, β-casein, ovalbumin, and bovine serum albumin) and compared with those of titanium arsenate-modified silica nanoparticles (TiAs-SNPs). The results showed that more selective enrichment of multiply phosphorylated peptides was observed with ZrAs-SNPs than with TiAs-SNPs whereas TiAs-SNPs resulted in slightly better recovery of singly phosphorylated peptides. ZrAs-SNPs were chosen for direct capture of phosphopeptides from diluted human serum of healthy and adenocarcinoma individuals. Our experimental profiling of serum phosphopeptides revealed that the level of phosphorylated fibrinogen peptide A was up-regulated in the serum of adenocarcinoma patients in comparison with healthy adults. This suggests the possibility of using ZrAs-SNPs for discovery of biomarkers of the pathogenesis process of tumors.


ZrAs-SNPs with trapped phosphopeptides


Zirconium arsenate-modified silica nanoparticles Phosphopeptide enrichment Singly/multiply phosphorylated peptides Human serum MALDI MS 


  1. 1.
    Graves JD, Krebs EG (1999) Pharmacol Ther 82:111–121CrossRefGoogle Scholar
  2. 2.
    Hunter T (2000) Cell 100:113–127CrossRefGoogle Scholar
  3. 3.
    Mann M, Ong SE, Gronborg M, Steen H, Jensen ON, Pandey A (2002) Trends Biotechnol 20:261–268CrossRefGoogle Scholar
  4. 4.
    McLachlin DT, Chait BT (2001) Curr Opin Chem Biol 5:591–602CrossRefGoogle Scholar
  5. 5.
    Schweppe RE, Haydon CE, Lewis TA, Resing KA, Ahn NG (2003) Acc Chem Res 36:453–461CrossRefGoogle Scholar
  6. 6.
    Collins MO, Yu L, Choudhary JS (2007) Proteomics 7:2751–2768CrossRefGoogle Scholar
  7. 7.
    Xu XQ, Deng CH, Gao MX, Yu WJ, Yang PY, Zhang XM (2006) Adv Mater 18:3289–3293CrossRefGoogle Scholar
  8. 8.
    Pan CS, Ye ML, Liu YG, Feng S, Jiang XG, Han GH, Zhu JJ, Zou HF (2006) J Proteome Res 5:3114–3124CrossRefGoogle Scholar
  9. 9.
    Dunn JD, Watson JT, Bruening ML (2006) Anal Chem 78:1574–1580CrossRefGoogle Scholar
  10. 10.
    Tsai CF, Wang YT, Chen YR, Lai CY, Lin PY, Pan KT, Chen JY, Khoo KH, Chen YJ (2008) J Proteome Res 7:4058–4069CrossRefGoogle Scholar
  11. 11.
    Ficarro SB, McCleland ML, Stukenberg PT, Burke DJ, Burke DJ, Ross MM, Shabanowitz J, Hunt DF, White FM (2002) Nat Biotechnol 20:301–306CrossRefGoogle Scholar
  12. 12.
    Brill LM, Salomon AR, Ficarro SB, Mukherji M, Stettler-Gill M, Peters EC (2004) Anal Chem 76:2763–2772CrossRefGoogle Scholar
  13. 13.
    Feng S, Ye ML, Zhou HJ, Jiang XG, Jiang XN, Zou HF, Gong BL (2007) Mol Cell Proteomics 6:1656–1665CrossRefGoogle Scholar
  14. 14.
    Zhou HJ, Ye ML, Dong J, Han GH, Jiang XN, Wu RN, Zou HF (2008) J Proteome Res 7:3957–3967CrossRefGoogle Scholar
  15. 15.
    Wu J-H, Zhao Y, Li T, Xu C, Xiao K, Feng Y-Q, Guo L (2010) J Sep Sci 33:1806–1815CrossRefGoogle Scholar
  16. 16.
    Kweon HK, Hakansson K (2006) Anal Chem 78:1743–1749CrossRefGoogle Scholar
  17. 17.
    Li Y, Xu XQ, Qi DW, Deng CH, Yang PY, Zhang XM (2008) J Proteome Res 7:2526–2538CrossRefGoogle Scholar
  18. 18.
    Yu ZY, Han GH, Sun ST, Jiang XN, Chen R, Wang FJ, Wu RA, Ye ML, Zou HF (2009) Anal Chim Acta 636:34–41CrossRefGoogle Scholar
  19. 19.
    Zhou HJ, Xu SY, Ye ML, Feng S, Pan CS, Jiang XG, Li X, Han GH, Fu Y, Zou HF (2006) J Proteome Res 5:2431–2437CrossRefGoogle Scholar
  20. 20.
    Zhao P-X, Zhao Y, Guo X-F, Wang H, Zhang H-S (2011) J Chromatogr A 1218:2528–2539CrossRefGoogle Scholar
  21. 21.
    Claassen A (1942) Chem Zentr 1:3124Google Scholar
  22. 22.
    Richter F (1941) Z Anal Chem 121:1–16CrossRefGoogle Scholar
  23. 23.
    Larsson PO, Glad M, Hansson L, Mansson MO, Ohlson S, Mosbach K (1983) Adv Chromatogr 21:41–85Google Scholar
  24. 24.
    Stanghellini PL, Boccaleri E, Diana E, Alberti G, Vivani R (2004) Inorg Chem 43:5698–5703CrossRefGoogle Scholar
  25. 25.
    Nonglaton G, Benitez IO, Guisle I, Pipelier M, Leger J, Dubreuil D, Tellier C, Talham DR, Bujoli B (2004) J Am Chem Soc 126:1497–1502CrossRefGoogle Scholar
  26. 26.
    Larsen MR, Thingholm TE, Jensen ON, Roepstorff P, Jorgensen TJD (2005) Mol Cell Proteomics 4:873–886CrossRefGoogle Scholar
  27. 27.
    Stensballe A, Jensen ON (2004) Rapid Commun Mass Spectrom 18:1721–1730CrossRefGoogle Scholar
  28. 28.
    Hart SR, Waterfield MD, Burlingame AL, Cramer R (2002) J Am Soc Mass Spectrom 13:1042–1051CrossRefGoogle Scholar
  29. 29.
    Petricoin EF, Belluco C, Araujo RP, Liotta LA (2006) Nat Rev Cancer 6:961–967CrossRefGoogle Scholar
  30. 30.
    Hu LH, Zhou HJ, Li YH, Sun ST, Guo LH, Ye ML, Tian XF, Gu JR, Yang SL, Zou HF (2009) Anal Chem 81:94–104CrossRefGoogle Scholar
  31. 31.
    Li Y, Qi DW, Deng CH, Yang PY, Zhang XM (2008) J Proteome Res 7:1767–1777CrossRefGoogle Scholar
  32. 32.
    Theodorescu D, Wittke S, Ross MM, Walden M, Conaway M, Just I, Mischak H, Frierson HF (2006) Lancet Oncol 7:230–240CrossRefGoogle Scholar
  33. 33.
    Ogata Y, Hepplmann CJ, Charlesworth MC, Madden BJ, Miller MN, Kalli KR, Cilby WA, Bergen HR, Saggese DA, Muddiman DC (2006) J Proteome Res 5:3318–3325CrossRefGoogle Scholar
  34. 34.
    Orvisky E, Drake SK, Martin BM, Abdel-Hamid M, Ressom HW, Varghese RS, An Y, Saha D, Hortin GL, Loffredo CA, Goldman R (2006) Proteomics 6:2895–2902CrossRefGoogle Scholar
  35. 35.
    Ebert MPA, Niemeyer D, Deininger SO, Wex T, Knippig C, Hoffmann J, Sauer J, Albrecht W, Malfertheiner P, Rocken C (2006) J Proteome Res 5:2152–2158CrossRefGoogle Scholar
  36. 36.
    Seydewitz HH, Matthias FR, Schondorf TH, Witt I (1987) Thromb Res 46:437–445CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Pei-Xuan Zhao
    • 1
  • Xiao-Feng Guo
    • 1
  • Hong Wang
    • 1
  • Chu-Bo Qi
    • 2
  • He-Shun Xia
    • 2
  • Hua-Shan Zhang
    • 1
  1. 1.Department of Chemistry, Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education)Wuhan UniversityWuhanChina
  2. 2.Department of PathologyHubei Cancer HospitalWuhanChina

Personalised recommendations