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Development and Applications of the Lectin Microarray

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SialoGlyco Chemistry and Biology II

Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 367))

Abstract

The lectin microarray is an emerging technology for glycomics. It has already found maximum use in diverse fields of glycobiology by providing simple procedures for differential glycan profiling in a rapid and high-throughput manner. Since its first appearance in the literature in 2005, many application methods have been developed essentially on the same platform, comprising a series of glycan-binding proteins immobilized on an appropriate substrate such as a glass slide. Because the lectin microarray strategy does not require prior liberation of glycans from the core protein in glycoprotein analysis, it should encourage researchers not familiar with glycotechnology to use glycan analysis in future work. This feasibility should provide a broader range of experimental scientists with good opportunities to investigate novel aspects of glycoscience. Applications of the technology include not only basic sciences but also the growing fields of bio-industry. This chapter describes first the essence of glycan profiling and the basic fabrication of the lectin microarray for this purpose. In the latter part the focus is on diverse applications to both structural and functional glycomics, with emphasis on the wide applicability now available with this new technology. Finally, the importance of developing advanced lectin engineering is discussed.

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References

  1. Varki A (1993) Biological roles of oligosaccharides: all of the theories are correct. Glycobiology 3:97–130

    Article  CAS  Google Scholar 

  2. Varki A, Lowe JB (2009) Biological roles of glycans. In: Varki A, Cummings RD, Esko JD, Freeze HH, Stanley P, Bertozzi CR, Hart GW, Etzler ME (eds) Essentials of glycobiology, 2nd edn. Cold Spring Harbor, New York

    Google Scholar 

  3. Laine RA (1994) A calculation of all possible oligosaccharide isomers both branched and linear yields 1.05 x 1012 structures for a reducing hexasaccharide: the isomer barrier to development of single-method saccharide sequencing or synthesis systems. Glycobiology 4:759–767

    Article  CAS  Google Scholar 

  4. Hirabayashi J (2008) Concept, strategy and realization of lectin-based glycan profiling. J Biochem 144:139–147

    Article  CAS  Google Scholar 

  5. Hirabayashi J, Kuno A, Tateno H (2011) Lectin-based structural glycomics: a practical approach to complex glycans. Electrophoresis 32:1118–1128

    Article  CAS  Google Scholar 

  6. Ito H, Kuno A, Sawaki H, Sogabe M, Ozaki H, Tanaka Y, Mizokami M, Shoda JI, Angata T, Sato T, Hirabayashi J, Ikehara Y, Narimatsu H (2009) Strategy for glycoproteomics: identification of glyco-alteration using multiple glycan profiling tools. J Proteome Res 8:1358–1367

    Article  CAS  Google Scholar 

  7. Narimatsu H, Narimatsu H, Sawaki H, Kuno A, Kaji H, Ito H, Ikehara Y (2010) A strategy for discovery of cancer glyco-biomarkers in serum using newly developed technologies for glycoproteomics. FEBS J 277:95–105

    Article  CAS  Google Scholar 

  8. Angeloni S, Ridet JL, Kusy N, Gao H, Crevoisier F, Guinchard S, Kochhar S, Sigrist H, Sprenger N (2005) Glycoprofiling with micro-arrays of glycoconjugates and lectins. Glycobiology 15:31–41

    Article  CAS  Google Scholar 

  9. Pilobello KT, Krishnamoorthy L, Slawek D, Mahal LK (2005) Development of a lectin microarray for the rapid analysis of protein glycopatterns. Chembiochem 6:985–989

    Article  CAS  Google Scholar 

  10. Kuno A, Uchiyama N, Koseki-Kuno S, Ebe Y, Takashima S, Yamada M, Hirabayashi J (2005) Evanescent-field fluorescence-assisted lectin microarray: a new strategy for glycan profiling. Nat Methods 2:851–856

    Article  CAS  Google Scholar 

  11. Zheng T, Peelen D, Smith LM (2005) Lectin arrays for profiling cell surface carbohydrate expression. J Am Chem Soc 127:9982–9983

    Article  CAS  Google Scholar 

  12. Rosenfeld R, Bangio H, Gerwig GJ, Rosenberg R, Aloni R, Cohen Y, Amor Y, Plaschkes I, Kamerling JP, Maya RB (2007) A lectin array-based methodology for the analysis of protein glycosylation. J Biochem Biophys Methods 70:415–426

    Article  CAS  Google Scholar 

  13. Tao SC, Li Y, Zhou J, Qian J, Schnaar RL, Zhang Y, Goldstein IJ, Zhu H, Schneck JP (2008) Lectin microarray: a powerful tool for glycan related biomarker discovery. Glycobiology 18:761–769

    Article  CAS  Google Scholar 

  14. Hirabayashi J, Arata Y, Kasai K (2001) Glycome project: concept, strategy and preliminary application to Caenorhabditis elegans. Proteomics 1:295–303

    Article  CAS  Google Scholar 

  15. Hirabayashi J (2004) Lectin-based structural glycomics: glycoproteomics and glycan profiling. Glycoconj J 21:35–40

    Article  Google Scholar 

  16. Kuno A, Ikehara Y, Tanaka Y, Angata T, Unno S, Sogabe M, Ozaki H, Ito K, Hirabayashi J, Mizokami M, Narimatsu H (2011) Multilectin assay for detecting fibrosis-specific glyco-alteration by means of lectin microarray. Clin Chem 57:48–56

    Article  CAS  Google Scholar 

  17. Kuno A, Ikehara Y, Tanaka Y, Saito K, Ito K, Tsuruno C, Nagai S, Takahama Y, Mizokami M, Hirabayashi J, Narimatsu H (2011) LecT-Hepa: a triplex lectin-antibody sandwich immunoassay for estimating the progression dynamics of liver fibrosis assisted by a bedside clinical chemistry analyzer and an automated pretreatment machine. Clin Chim Acta 412:1767–1772

    Article  CAS  Google Scholar 

  18. Gupta G, Surolia A, Sampathkumar SG (2010) Lectin microarrays for glycomic analysis. OMICS 14:419–436

    Article  CAS  Google Scholar 

  19. Katrlík J, Svitel J, Gemeiner P, Kozár T, Tkac J (2010) Glycan and lectin microarrays for glycomics and medicinal applications. Med Res Rev 30:394–418

    Google Scholar 

  20. Vanderschaeghe D, Festjens N, Delanghe J, Callewaert N (2010) Glycome profiling using modern glycomics technology: technical aspects and applications. Biol Chem 391:149–161

    Article  CAS  Google Scholar 

  21. Rakus JF, Mahal LK (2011) New technologies for glycomic analysis: toward a systematic understanding of the glycome. Annu Rev Anal Chem (Palo Alto Calif) 4:367–392

    Article  CAS  Google Scholar 

  22. Goldstein IJ, Hughes RC, Monsigny M, Osawa T, Sharon N (1980) What should be called a lectin? Nature 285:66

    Article  Google Scholar 

  23. Fukui S, Feizi T, Galustian C, Lawson AM, Chai W (2002) Nat Biotechnol 20:1011–1107

    Article  CAS  Google Scholar 

  24. Blixt O, Head S, Mondala T, Scanlan C, Huflejt ME, Alvarez R, Bryan MC, Fazio F, Calarese D, Stevens J, Razi N, Stevens DJ, Skehel JJ, van Die I, Burton DR, Wilson IA, Cummings R, Bovin N, Wong CH, Paulson JC (2004) Printed covalent glycan array for ligand profiling of diverse glycan binding proteins. Proc Natl Acad Sci U S A 101:17033–17038

    Article  CAS  Google Scholar 

  25. Tateno H, Mori A, Uchiyama N, Yabe R, Iwaki J, Shikanai T, Angata T, Narimatsu H, Hirabayashi J (2008) Glycoconjugate microarray based on an evanescent-field fluorescence-assisted detection principle for investigation of glycan-binding proteins. Glycobiology 18:789–798

    Article  CAS  Google Scholar 

  26. Angata T (2006) Molecular diversity and evolution of the Siglec family of cell-surface lectins. Mol Divers 10:555–566

    Article  CAS  Google Scholar 

  27. Barondes SH, Castronovo V, Cooper DN, Cummings RD, Drickamer K, Feizi T, Gitt MA, Hirabayashi J, Hughes C, Kasai K, Leffler H, Liu F-T, Lotan R, Mercurio AM, Monsigny M, Pillai S, Poirer F, Raz A, Rigby PWJ, Rini JM, Wang JL (1994) Galectins: a family of animal beta-galactoside-binding lectins. Cell 76:597–598

    Article  CAS  Google Scholar 

  28. Kuno A, Kato Y, Matsuda A, Kaneko MK, Ito H, Amano K, Chiba Y, Narimatsu H, Hirabayashi J (2008) Focused differential glycan analysis with the platform antibody-assisted lectin profiling for glycan-related biomarker verification. Mol Cell Proteomics 8:99–108

    Article  Google Scholar 

  29. Ogata S, Muramatsu T, Kobata A (1975) Fractionation of glycopeptides by affinity column chromatography on concanavalin A-Sepharose. J Biochem 78:687–696

    CAS  Google Scholar 

  30. Cummings RD, Kornfeld S (1982) Characterization of the structural determinants required for the high affinity interaction of asparagine-linked oligosaccharides with immobilized Phaseolus vulgaris leukoagglutinating and erythroagglutinating lectins. J Biol Chem 257:11235–11240

    CAS  Google Scholar 

  31. Kasai K, Oda Y, Nishikata M, Ishii S (1986) Frontal affinity chromatography: theory for its application to studies on specific interactions of biomolecules. J Chromatogr 376:33–47

    Article  CAS  Google Scholar 

  32. Nakamura-Tsuruta S, Uchiyama N, Hirabayashi J (2006) High-throughput analysis of lectin-oligosaccharide interactions by automated frontal affinity chromatography. Methods Enzymol 415:311–325

    Article  CAS  Google Scholar 

  33. Tateno H, Nakamura-Tsuruta S, Hirabayashi J (2007) Frontal affinity chromatography: sugar-protein interactions. Nat Protoc 2:2529–2537

    Article  CAS  Google Scholar 

  34. Uchiyama N, Kuno A, Tateno H, Kubo Y, Mizuno M, Noguchi M, Hirabayashi J (2008) Optimization of evanescent-field fluorescence-assisted lectin microarray for high-sensitivity detection of monovalent oligosaccharides and glycoproteins. Proteomics 8:3042–3050

    Article  CAS  Google Scholar 

  35. Lee RT, Lee YC (2000) Affinity enhancement by multivalent lectin-carbohydrate interaction. Glycoconj J 17:543–551

    Article  CAS  Google Scholar 

  36. Brewer CF, Miceli MC, Baum LG (2002) Clusters, bundles, arrays and lattices: novel mechanisms for lectin-saccharide-mediated cellular interactions. Curr Opin Struct Biol 12:616–623

    Article  CAS  Google Scholar 

  37. Yamada M (2009) Lectin microarrays. In: Matson RS (ed) Microarray methods and protocols. CRC Press, Taylor & Francis Group, Boca Raton, pp 139–154

    Google Scholar 

  38. Koshi Y, Nakata E, Yamane H, Hamachi I (2006) A fluorescent lectin array using supramolecular hydrogel for simple detection and pattern profiling for various glycoconjugates. J Am Chem Soc 128:10413–10422

    Article  CAS  Google Scholar 

  39. Abbas A, Linman MJ, Cheng Q (2011) New trends in instrumental design for surface plasmon resonance-based biosensors. Biosens Bioelectron 26:1815–1824

    Article  CAS  Google Scholar 

  40. Tateno H, Kuno A, Hirabayashi J (2008) How to determine specificity: from lectin profiling to glycan profiling. In: Gabius H-J (ed) Sugar code: fundamentals of glycoscience. Willey, Weinheim, pp 247–259

    Google Scholar 

  41. Hirabayashi J (2009) In: Pierce M, Cummings R (eds) Handbook of glycomics. Elsevier, Amsterdam, pp 161–176

    Google Scholar 

  42. Kuno A, Itakura Y, Toyoda M, Takahashi Y, Yamada M, Umezawa A, Hirabayashi J (2008) Development of a data-mining system for differential profiling of cell glycoproteins based on lectin microarray. J Proteomics Bioinform 1:68–72

    Article  CAS  Google Scholar 

  43. Kuno A, Matsuda A, Ikehara Y, Narimatsu H, Hirabayashi J (2010) Differential glycan profiling by lectin microarray targeting tissue specimens. Methods Enzymol 478:165–179

    Article  CAS  Google Scholar 

  44. Tateno H, Kuno A, Itakura Y, Hirabayashi J (2010) A versatile technology for cellular glycomics using lectin microarray. Methods Enzymol 478:181–195

    Article  CAS  Google Scholar 

  45. Toyoda M, Yamazaki-Inoue M, Itakura Y, Kuno A, Ogawa T, Yamada M, Akutsu H, Takahashi Y, Kanzaki S, Narimatsu H, Hirabayashi J, Umezawa A (2011) Lectin microarray analysis of pluripotent and multipotent stem cells. Genes Cells 16:1–11

    Article  CAS  Google Scholar 

  46. Tateno H, Toyoda M, Saito S, Onuma Y, Ito Y, Hiemori K, Fukumura M, Nakasu A, Nakanishi M, Ohnuma K, Akutsu H, Umezawa A, Horimoto K, Hirabayashi J, Asashima M (2011) Glycome diagnosis of human induced pluripotent stem cells using lectin microarray. J Biol Chem 286:20345–20353

    Article  CAS  Google Scholar 

  47. Saito S, Onuma Y, Ito Y, Tateno H, Toyoda M, Akutsu H, Nishino K, Chikazawa E, Fukawatase Y, Miyagawa Y, Okita H, Kiyokawa N, Shimma Y, Umezawa A, Hirabayashi J, Horimoto K, Asashima M (2011) Possible linkages between the inner and outer cellular states of human induced pluripotent stem cells. BMC Syst Biol 5(Suppl):S17

    Article  CAS  Google Scholar 

  48. Matsuda A, Kuno A, Ishida H, Kawamoto T, Shoda J, Hirabayashi J (2008) Development of an all-in-one technology for glycan profiling targeting formalin-embedded tissue sections. Biochem Biophys Res Commun 370:259–263

    Article  CAS  Google Scholar 

  49. Matsuda A, Kuno A, Kawamoto T, Matsuzaki H, Irimura T, Ikehara Y, Zen Y, Nakanuma Y, Yamamoto M, Ohkohchi N, Shoda J, Hirabayashi J, Narimatsu H (2010) Wisteria floribunda agglutinin-positive mucin 1 is a sensitive biliary marker for human cholangiocarcinoma. Hepatology 52:174–182

    Article  CAS  Google Scholar 

  50. Gustafsson A, Sjöblom M, Strindelius L, Johansson T, Fleckenstein T, Chatzissavidou N, Lindberg L, Angström J, Rova U, Holgersson J (2011) Pichia pastoris-produced mucin-type fusion proteins with multivalent O-glycan substitution as targeting molecules for mannose-specific receptors of the immune system. Glycobiology 21:1071–1086

    Article  CAS  Google Scholar 

  51. Huang W, Wang D, Yamada M, Wang LX (2009) Chemoenzymatic synthesis and lectin array characterization of a class of N-glycan clusters. J Am Chem Soc 131:17963–17971

    Article  CAS  Google Scholar 

  52. Amano K, Chiba Y, Kasahara Y, Kato Y, Kaneko MK, Kuno A, Ito H, Kobayashi K, Hirabayashi J, Jigami Y, Narimatsu H (2008) Engineering of mucin-type human glycoproteins in yeast cells. Proc Natl Acad Sci U S A 105:3232–3237

    Article  CAS  Google Scholar 

  53. Miyagawa S, Takeishi S, Yamamoto A, Ikeda K, Matsunari H, Yamada M, Okabe M, Miyoshi E, Fukuzawa M, Nagashima H (2010) Survey of glycoantigens in cells from α1-3galactosyltransferase knockout pig using a lectin microarray. Xenotransplantation 17:61–70

    Article  Google Scholar 

  54. Suen KF, Turner MS, Gao F, Liu B, Althage A, Slavin A, Ou W, Zuo E, Eckart M, Ogawa T, Yamada M, Tuntland T, Harris JL, Trauger JW (2010) Transient expression of an IL-23R extracellular domain Fc fusion protein in CHO vs. HEK cells results in improved plasma exposure. Protein Expr Purif 71:96–102

    Article  CAS  Google Scholar 

  55. Nakagawa T, Takeishi S, Kameyama A, Yagi H, Yoshioka T, Moriwaki K, Masuda T, Matsumoto H, Kato K, Narimatsu H, Taniguchi N, Miyoshi E (2010) Glycomic analyses of glycoproteins in bile and serum during rat hepatocarcinogenesis. J Proteome Res 9:4888–4896

    Article  CAS  Google Scholar 

  56. Kondoh G, Watanabe H, Tashima Y, Maeda Y, Kinoshita T (2009) Testicular angiotensin-converting enzyme with different glycan modification: characterization on glycosylphosphatidylinositol-anchored protein releasing and dipeptidase activities. J Biochem 145:115–121

    Article  CAS  Google Scholar 

  57. Togayachi A, Kozono Y, Ishida H, Abe S, Suzuki N, Tsunoda Y, Hagiwara K, Kuno A, Ohkura T, Sato N, Sato T, Hirabayashi J, Ikehara Y, Tachibana K, Narimatsu H (2007) Polylactosamine on glycoproteins influences basal levels of lymphocyte and macrophage activation. Proc Natl Acad Sci U S A 104:15829–15834

    Article  CAS  Google Scholar 

  58. Kaneko MK, Kato Y, Kameyama A, Ito H, Kuno A, Hirabayashi J, Kubota T, Amano K, Chiba Y, Hasegawa Y, Sasagawa I, Mishima K, Narimatsu H (2007) Functional glycosylation of human podoplanin: glycan structure of platelet aggregation-inducing factor. FEBS Lett 581:331–336

    Article  CAS  Google Scholar 

  59. Futakawa S, Nara K, Miyajima M, Kuno A, Ito H, Kaji H, Shirotani K, Honda T, Tohyama Y, Hoshi K, Hanzawa Y, Kitazume S, Imamaki R, Furukawa K, Tasaki K, Arai H, Yuasa T, Abe M, Arai H, Narimatsu H, Hashimoto Y (2011) A unique N-glycan on human transferrin in CSF: a possible biomarker for iNPH. Neurobiol Aging 33(8):1807–1815

    Article  Google Scholar 

  60. Fry SA, Afrough B, Lomax-Browne HJ, Timms JF, Velentzis LS, Leathem AJ (2011) Lectin microarray profiling of metastatic breast cancers. Glycobiology 21:1060–1070

    Article  CAS  Google Scholar 

  61. Kuwamoto K, Takeda Y, Shirai A, Nakagawa T, Takeishi S, Ihara S, Miyamoto Y, Shinzaki S, Ko JH, Miyoshi E (2010) Identification of various types of α2-HS glycoprotein in sera of patients with pancreatic cancer: possible implication in resistance to protease treatment. Mol Med Report 3:651–656

    CAS  Google Scholar 

  62. Sasaki N, Moriwaki K, Uozumi N, Noda K, Taniguchi N, Kameyama A, Narimatsu H, Takeishi S, Yamada M, Koyama N, Miyoshi E (2009) High levels of E4-PHA-reactive oligosaccharides: potential as marker for cells with characteristics of hepatic progenitor cells. Glycoconj J 26:1213–1223

    Article  CAS  Google Scholar 

  63. Krishnamoorthy L, Bess JW Jr, Preston AB, Nagashima K, Mahal LK (2009) HIV-1 and microvesicles from T cells share a common glycome, arguing for a common origin. Nat Chem Biol 5:244–250

    Article  CAS  Google Scholar 

  64. Hsu KL, Pilobello KT, Mahal LK (2006) Analyzing the dynamic bacterial glycome with a lectin microarray approach. Nat Chem Biol 2:153–157

    Article  CAS  Google Scholar 

  65. Ebe Y, Kuno A, Uchiyama N, Koseki-Kuno S, Yamada M, Sato T, Narimatsu H, Hirabayashi J (2006) Application of lectin microarray to crude samples: differential glycan profiling of lec mutants. J Biochem 139:323–327

    Article  CAS  Google Scholar 

  66. Tateno H, Uchiyama N, Kuno A, Togayachi A, Sato T, Narimatsu H, Hirabayashi J (2007) A novel strategy for mammalian cell surface glycome profiling using lectin microarray. Glycobiology 17:1138–1146

    Article  CAS  Google Scholar 

  67. Yasuda M, Tateno H, Hirabayashi T, Iino T, Sako T (2011) Lectin microarray reveals binding profiles of Lactobacillus casei strains in a comprehensive analysis of bacterial cell wall polysaccharides. Appl Environ Microbiol 77:4539–4546

    Article  CAS  Google Scholar 

  68. Pilobello KT, Slawek DE, Mahal LK (2007) A ratiometric lectin microarray approach to analysis of the dynamic mammalian glycome. Proc Natl Acad Sci U S A 104:11534–11539

    Article  CAS  Google Scholar 

  69. Tonge R, Shaw J, Middleton B, Rowlinson R, Rayner S, Young J, Pognan F, Hawkins E, Currie I, Davison M (2001) Validation and development of fluorescence two-dimensional differential gel electrophoresis proteomics technology. Proteomics 1:377–396

    Article  CAS  Google Scholar 

  70. Propheter DC, Hsu KL, Mahal LK (2011) Recombinant lectin microarrays for glycomic analysis. Methods Mol Biol 723:67–77

    Article  CAS  Google Scholar 

  71. Yabe R, Suzuki R, Kuno A, Fujimoto Z, Jigami Y, Hirabayashi J (2007) Tailoring a novel sialic acid-binding lectin from a ricin-B chain-like galactose-binding protein by natural evolution-mimicry. J Biochem 141:389–399

    Article  CAS  Google Scholar 

  72. Hu D, Tateno H, Kuno A, Yabe R, Hirabayashi J (2012) Directed evolution of lectins with sugar-binding specificity for 6-sulfo-galactose. J Biol Chem 287:20313–20320

    Article  CAS  Google Scholar 

  73. Hu D, Tateno H, Sato T, Narimatsu H, Hirabayashi J (2013) Tailoring GalNAcα1-3Galβ-specific lectins from a multi-specific fungal galectin: dramatic change of carbohydrate specificity by a single amino-acid substitution. Biochem J 453:261–270

    Article  CAS  Google Scholar 

  74. Bicker KL, Sun J, Lavigne JJ, Thompson PR (2011) Boronic acid functionalized peptidyl synthetic lectins: combinatorial library design, peptide sequencing, and selective glycoprotein recognition. ACS Comb Sci 13:232–243

    Article  CAS  Google Scholar 

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Hirabayashi, J., Kuno, A., Tateno, H. (2014). Development and Applications of the Lectin Microarray. In: Gerardy-Schahn, R., Delannoy, P., von Itzstein, M. (eds) SialoGlyco Chemistry and Biology II. Topics in Current Chemistry, vol 367. Springer, Cham. https://doi.org/10.1007/128_2014_612

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