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Boronic acid functionalized MOFs as HILIC material for N-linked glycopeptide enrichment

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Abstract

Highly specific enrichment of N-linked glycopeptides from complex biological samples is crucial prior to mass spectrometric analysis. In this work, a hydrophilic metal–organic framework composite is prepared by the growth of UiO-66-NH2 on graphene sheets, followed by its post-synthetic modification to attach boronic acid to form GO@UiO-66-PBA. The fabrication of graphene oxide-MOF composite results in enhanced surface area with improved thermal and chemical stability. The synthesized MOF nanocomposite is characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and BET. A crystalline structure with high porosity offering large surface area and good hydrophilicity of the nanocomposite assists as an enrichment tool in glycoproteomics. The GO@UiO-66-PBA nanocomposite selectively enriches N-linked glycopeptides from tryptic digests of horseradish peroxidase (HRP) and immunoglobulin (IgG). GO@UiO-66-PBA nanoparticles show a low detection limit (1 fmol) and good specificity (1:200), reusability and reproducibility for N-linked glycopeptide enrichment from IgG digest. The binding capacity of GO@UiO-66-PBA is 84 mg/g for protein concentration, with a good recovery of 86.5%. A total of 372 N-linked glycopeptides corresponding to different glycoproteins are identified from only 1 μL of human serum digest. Thus, the presented research work can be an efficient separation platform for N-linked glycopeptide enrichment from complex samples, which can be extended to cost-effective routine analysis.

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References

  1. Ohtsubo K, Marth JD. Glycosylation in cellular mechanisms of health and disease. Cell J. 2006;126(5):855–67. https://doi.org/10.1016/j.cell.2006.08.019.

    Article  CAS  Google Scholar 

  2. Dennis JW, Nabi IR, Demetriou M. Metabolism, cell surface organization, and disease. Cell J. 2009;139(7):1229–41. https://doi.org/10.1016/j.cell.2009.12.008.

    Article  Google Scholar 

  3. Yang X, Ongusaha PP, Miles PD, Havstad JC, Zhang F, So WV, et al. Phosphoinositide signalling links O-GlcNAc transferase to insulin resistance. Nature. 2008;451(7181):964. https://doi.org/10.1038/nature06668.

    Article  CAS  PubMed  Google Scholar 

  4. Mariño K, Bones J, Kattla JJ, Rudd PM. A systematic approach to protein glycosylation analysis: a path through the maze. Nat Chem Biol. 2010;6(10):713. https://doi.org/10.1038/nchembio.437.

    Article  CAS  PubMed  Google Scholar 

  5. Hahne H, Neubert P, Kuhn K, Etienne C, Bomgarden R, Rogers JC, et al. Carbonyl-reactive tandem mass tags for the proteome-wide quantification of N-linked glycans. Anal Chem. 2012;84(8):3716–24. https://doi.org/10.1021/ac300197c.

    Article  CAS  PubMed  Google Scholar 

  6. Christiansen MN, Chik J, Lee L, Anugraham M, Abrahams JL, Packer NH. Cell surface protein glycosylation in cancer. Proteomics. 2014;14(4-5):525–46. https://doi.org/10.1002/pmic.201300387.

    Article  CAS  PubMed  Google Scholar 

  7. Chen D, Hu Y-N, Hussain D, Zhu G-T, Huang Y-Q, Feng Y-Q. Electrospun fibrous thin film microextraction coupled with desorption corona beam ionization-mass spectrometry for rapid analysis of antidepressants in human plasma. Talanta. 2016;152:188–95. https://doi.org/10.1016/j.talanta.2016.02.003.

    Article  CAS  PubMed  Google Scholar 

  8. Sajid MS, Jabeen F, Hussain D, Ashiq MN, Najam-ul-Haq M. Hydrazide-functionalized affinity on conventional support materials for glycopeptide enrichment. Anal Bioanal Chem. 2017;409(12):3135–43. https://doi.org/10.1007/s00216-017-0254-5.

    Article  CAS  PubMed  Google Scholar 

  9. Liu Y, Fu D, Yu L, Xiao Y, Peng X, Liang X. Oxidized dextran facilitated synthesis of a silica-based concanavalin a material for lectin affinity enrichment of glycoproteins/glycopeptides. J Chromatogr A. 2016;1455:147–55. https://doi.org/10.1016/j.chroma.2016.05.093.

    Article  CAS  PubMed  Google Scholar 

  10. Peng Y, Fu D, Zhang F, Yang B, Yu L, Liang X. A highly selective hydrophilic sorbent for enrichment of N-linked glycopeptides. J Chromatogr A. 2016;1460:197–201. https://doi.org/10.1016/j.chroma.2016.07.028.

    Article  CAS  PubMed  Google Scholar 

  11. Huang J, Wan H, Yao Y, Li J, Cheng K, Mao J, et al. Highly efficient release of glycopeptides from hydrazide beads by hydroxylamine assisted PNGase F deglycosylation for N-glycoproteome analysis. Anal Chem. 2015;87(20):10199–204. https://doi.org/10.1021/acs.analchem.5b02669.

    Article  CAS  PubMed  Google Scholar 

  12. Wang M, Zhang X, Deng C. Facile synthesis of magnetic poly (styrene-co-4-vinylbenzene-boronic acid) microspheres for selective enrichment of glycopeptides. Proteomics. 2015;15(13):2158–65. https://doi.org/10.1002/pmic.201300523.

    Article  CAS  PubMed  Google Scholar 

  13. Xu J, Zhang Z, He X-M, Wang R-Q, Hussain D, Feng Y-Q. Immobilization of zirconium-glycerolate nanowires on magnetic nanoparticles for extraction of urinary ribonucleosides. Microchim Acta. 2018;185(1):43. https://doi.org/10.1007/s00604-017-2596-2.

    Article  CAS  Google Scholar 

  14. Wu R, Li L, Deng C. Highly efficient and selective enrichment of glycopeptides using easily synthesized magG/PDA/Au/l-Cys composites. Proteomics. 2016;16(9):1311–20. https://doi.org/10.1002/pmic.201500383.

    Article  CAS  PubMed  Google Scholar 

  15. Mohyuddin A, Hussain D, Najam-ul-Haq M. Polydopamine assisted functionalization of boronic acid on magnetic nanoparticles for the selective extraction of ribosylated metabolites from urine. RSC Adv. 2017;7(16):9476–83. https://doi.org/10.1039/C6RA28369A.

    Article  CAS  Google Scholar 

  16. Li X-J, Jia M, Zhao Y-X, Liu Z-S, Aisa HA. Preparation of phenylboronate affinity rigid monolith with macromolecular porogen. J Chromatogr A. 2016;1438:171–8. https://doi.org/10.1016/j.chroma.2016.02.031.

    Article  CAS  PubMed  Google Scholar 

  17. Yao J, Wang J, Sun N, Deng C. One-step functionalization of magnetic nanoparticles with 4-mercaptophenylboronic acid for a highly efficient analysis of N-glycopeptides. Nanoscale. 2017;9(41):16024–9. https://doi.org/10.1039/C7NR04206J.

    Article  CAS  PubMed  Google Scholar 

  18. Wu C, Liang Y, Zhao Q, Qu Y, Zhang S, Wu Q, et al. Boronate affinity monolith with a gold nanoparticle-modified hydrophilic polymer as a matrix for the highly specific capture of glycoproteins. Chem Eur J. 2014;20(28):8737–43. https://doi.org/10.1002/chem.201402787.

    Article  CAS  PubMed  Google Scholar 

  19. Li Y, Wang J, Sun N, Deng C-H. Glucose-6-Phosphate-Functionalized magnetic microsphere as novel hydrophilic probe for specific capture of N-linked glycopeptides. Anal Chem. 2017;89(20):11151–8. https://doi.org/10.1021/acs.analchem.7b03708.

    Article  CAS  PubMed  Google Scholar 

  20. Liu L, Zhang Y, Zhang L, Yan G, Yao J, Yang P, et al. Highly specific revelation of rat serum glycopeptidome by boronic acid-functionalized mesoporous silica. Anal Chem. 2012;753:64–72. https://doi.org/10.1016/j.aca.2012.10.002.

    Article  CAS  Google Scholar 

  21. Sun N, Wang J, Yao J, Deng C. Hydrophilic mesoporous silica materials for highly specific enrichment of N-linked glycopeptide. Anal Chem. 2017;89(3):1764–71. https://doi.org/10.1021/acs.analchem.6b04054.

    Article  CAS  PubMed  Google Scholar 

  22. He C-T, Jiang L, Ye Z-M, Krishna R, Zhong Z-S, Liao P-Q, et al. Exceptional hydrophobicity of a large-pore metal–organic zeolite. J. Am. Chem. Soc. 2015;137(22):7217–23. https://doi.org/10.1021/jacs.5b03727.

    Article  CAS  PubMed  Google Scholar 

  23. Zhang W, Lu G, Cui C, Liu Y, Li S, Yan W, et al. A family of metal-organic frameworks exhibiting size-selective catalysis with encapsulated noble-metal nanoparticles. Adv Mater. 2014;26(24):4056–60. https://doi.org/10.1002/adma.201400620.

    Article  CAS  PubMed  Google Scholar 

  24. Zhai Q-G, Bu X, Mao C, Zhao X, Feng P. Systematic and dramatic tuning on gas sorption performance in heterometallic metal–organic frameworks. J Am Chem Soc. 2016;138(8):2524–7. https://doi.org/10.1021/jacs.5b13491.

    Article  CAS  PubMed  Google Scholar 

  25. Yan Z, Zheng J, Chen J, Tong P, Lu M, Lin Z, et al. Preparation and evaluation of silica-UIO-66 composite as liquid chromatographic stationary phase for fast and efficient separation. J Chromatogr A. 2014;1366:45–53. https://doi.org/10.1016/j.chroma.2014.08.077.

    Article  CAS  PubMed  Google Scholar 

  26. Wu MX, Yang YW. Metal–organic framework (MOF)-based drug/cargo delivery and cancer therapy. Adv Mater. 2017;29(23):1606134. https://doi.org/10.1002/adma.201606134.

    Article  CAS  Google Scholar 

  27. Xia L, Liu L, Lv X, Qu F, Li G, You J. Towards the determination of sulfonamides in meat samples: A magnetic and mesoporous metal-organic framework as an efficient sorbent for magnetic solid phase extraction combined with high-performance liquid chromatography. J Chromatogr A. 2017;1500:24–31. https://doi.org/10.1016/j.chroma.2017.04.004.

    Article  CAS  PubMed  Google Scholar 

  28. Zhao M, Deng C, Zhang X. The design and synthesis of a hydrophilic core–shell–shell structured magnetic metal–organic framework as a novel immobilized metal ion affinity platform for phosphoproteome research. Chem Commun. 2014;50(47):6228–31. https://doi.org/10.1039/C4CC01038H.

    Article  CAS  Google Scholar 

  29. Saeed A, Hussain D, Saleem S, Mehdi S, Javeed R, Jabeen F, et al. Metal–organic framework-based affinity materials in proteomics. Anal Bioanal Chem. 2019;411(9):1745–59. https://doi.org/10.1007/s00216-019-01610-x.

    Article  CAS  PubMed  Google Scholar 

  30. Wang J, Li J, Wang Y, Gao M, Zhang X, Yang P. Development of versatile metal–organic framework functionalized magnetic graphene core–shell biocomposite for highly specific recognition of glycopeptides. ACS Appl Mater Interfaces. 2016;8(41):27482–9. https://doi.org/10.1021/acsami.6b08218.

    Article  CAS  PubMed  Google Scholar 

  31. Sun N, Wu H, Shen X, Deng C. Nanomaterials in Proteomics. Adv Funct Mater. 2019;1900253. https://doi.org/10.1002/adfm.201900253.

    Article  Google Scholar 

  32. Peng J, Zhang H, Li X, Liu S, Zhao X, Wu J, et al. Dual-metal centered zirconium–organic framework: a metal-affinity probe for highly specific interaction with phosphopeptides. ACS Appl Mater Interfaces. 2016;8(51):35012–20. https://doi.org/10.1021/acsami.6b12630.

    Article  CAS  PubMed  Google Scholar 

  33. Saeed A, Maya F, Xiao DJ, Najam-ul-Haq M, Svec F, Britt DK. Growth of a highly porous coordination polymer on a macroporous polymer monolith support for enhanced immobilized metal ion affinity chromatographic enrichment of phosphopeptides. Adv Funct Mater. 2014;24(37):5790–7. https://doi.org/10.1002/adfm.201400116.

    Article  CAS  Google Scholar 

  34. Yin P, Sun N, Deng C, Li Y, Zhang X, Yang P. Facile preparation of magnetic graphene double-sided mesoporous composites for the selective enrichment and analysis of endogenous peptides. Proteomics. 2013;13(15):2243–50. https://doi.org/10.1002/pmic.201300066.

    Article  CAS  PubMed  Google Scholar 

  35. Mohyuddin A, Hussain D, Fatima B, Athar M, Ashiq MN, Najam-ul-Haq M. Gallic acid functionalized UiO-66 for the recovery of ribosylated metabolites from human urine samples. Talanta. 2019;201:23–32. https://doi.org/10.1016/j.talanta.2019.03.072.

    Article  CAS  PubMed  Google Scholar 

  36. Yang Q, Zhu Y, Luo B, Lan F, Wu Y, Gu Z. pH-Responsive magnetic metal–organic framework nanocomposites for selective capture and release of glycoproteins. Nanoscale. 2017;9(2):527–32. https://doi.org/10.1039/C6NR08071E.

    Article  CAS  PubMed  Google Scholar 

  37. Gao Y, Ma D, Wang C, Guan J, Bao X. Reduced graphene oxide as a catalyst for hydrogenation of nitrobenzene at room temperature. ChemComm. 2011;47(8):2432–4. https://doi.org/10.1039/C0CC04420B.

    Article  CAS  Google Scholar 

  38. Cheng J-H, Chen Y-H, Yeh Y-S, Hy S, Kuo L-Y, Hwang B-J. Enhancement of Electrochemical Properties by Freeze-dried Graphene Oxide via Glucose-assisted Reduction. Electrochim Acta. 2016;197:146–51. https://doi.org/10.1016/j.electacta.2015.12.116.

    Article  CAS  Google Scholar 

  39. Szczęśniak B, Choma J, Jaroniec M. Ultrahigh benzene adsorption capacity of graphene-MOF composite fabricated via MOF crystallization in 3D mesoporous graphene. Microporous Mesoporous Mater. 2019;279:387–94. https://doi.org/10.1016/j.micromeso.2019.01.022.

    Article  CAS  Google Scholar 

  40. Hummers W, Offeman R. Functionalized Graphene and Graphene Oxide: Materials Synthesis. J Am Chem Soc. 1958;80:1339–44.

    Article  CAS  Google Scholar 

  41. Ma R, Hu J, Cai Z, Ju H. Facile synthesis of boronic acid-functionalized magnetic carbon nanotubes for highly specific enrichment of glycopeptides. Nanoscale. 2014;6(6):3150–6. https://doi.org/10.1039/C3NR05367A.

    Article  CAS  PubMed  Google Scholar 

  42. Li S, Li D, Sun L, Yao Y, Yao C. A designable aminophenylboronic acid functionalized magnetic Fe 3 O 4/ZIF-8/APBA for specific recognition of glycoproteins and glycopeptides. RSC Adv. 2018;8(13):6887–92. https://doi.org/10.1039/C7RA12054K.

    Article  CAS  Google Scholar 

  43. Liu B, Lu Y, Wang B, Yan Y, Liang H, Yang H. Facile Preparation of Hydrophilic Dual Functional Magnetic Metal-Organic Frameworks as a Platform for Proteomics Research. ChemistrySelect. 2019;4(7):2200–4. https://doi.org/10.1002/slct.201803527.

    Article  CAS  Google Scholar 

  44. Ma W, Xu L, Li Z, Sun Y, Bai Y, Liu H. Post-synthetic modification of an amino-functionalized metal–organic framework for highly efficient enrichment of N-linked glycopeptides. Nanoscale. 2016;8(21):10908–12. https://doi.org/10.1039/C6NR02490D.

    Article  CAS  PubMed  Google Scholar 

  45. Zhang Y-W, Li Z, Zhao Q, Zhou Y-L, Liu H-W, Zhang X-X. A facilely synthesized amino-functionalized metal–organic framework for highly specific and efficient enrichment of glycopeptides. ChemComm. 2014;50(78):11504–6. https://doi.org/10.1039/C4CC05179C.

    Article  CAS  Google Scholar 

  46. Liu Q. Deng C-h, Sun N. Hydrophilic tripeptide-functionalized magnetic metal–organic frameworks for the highly efficient enrichment of N-linked glycopeptides. Nanoscale. 2018;10(25):12149–55. https://doi.org/10.1039/C8NR03174F.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by the Higher Education Commission (HEC) of Pakistan.

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Authors and Affiliations

  1. Department of Chemistry, The Women University, Kutchery Campus, L.M.Q. Road, Multan, 66000, Pakistan

    Shafaq Saleem, Fahmida Jabeen & Adeela Saeed

  2. Institute of Chemical Sciences, Bahauddin Zakariya University, Multan, 60800, Pakistan

    Muhammad Salman Sajid, Dilshad Hussain, Fahmida Jabeen, Muhammad Najam-ul-Haq & Adeela Saeed

  3. International Centre for Chemical and Biological Sciences, HEJ Research Institute of Chemistry, University of Karachi, Karachi, 75270, Pakistan

    Dilshad Hussain

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  1. Shafaq Saleem
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Saleem, S., Sajid, M.S., Hussain, D. et al. Boronic acid functionalized MOFs as HILIC material for N-linked glycopeptide enrichment. Anal Bioanal Chem 412, 1509–1520 (2020). https://doi.org/10.1007/s00216-020-02427-9

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