A MALDI-MS-based quantitative glycoprofiling method on a 96-well plate platform

Kyoung-Jin Kim; Yoon-Woo Kim; Han-Gyu Park; Cheol-Hwan Hwang; In Young Park; Kwon-Young Choi; Yung-Hun Yang; Young Hwan Kim; Yun-Gon Kim

Journal of Industrial and Engineering Chemistry, Vol.46, 150-156, February, 2017

DOI10.1016/j.jiec.2016.10.025 Export Citation

A MALDI-MS-based quantitative glycoprofiling method on a 96-well plate platform

Kyoung-Jin Kim¹, Yoon-Woo Kim¹, Han-Gyu Park¹, Cheol-Hwan Hwang¹, In Young Park^{2, 3}, Kwon-Young Choi⁴, Yung-Hun Yang⁵, Young Hwan Kim^{2, 3, †}, and Yun-Gon Kim^{1, †}

¹Department of Chemical Engineering, Soongsil University, Seoul 156-743, South Korea
²Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon 305-764, South Korea
³Biomedical Omics Group, Korea Basic Science Institute (KBSI), Cheongju 363-883, South Korea
⁴Department of Environmental Engineering, College of Engineering, Ajou University, Suwon 443-749, South Korea
⁵Department of Microbial Engineering, College of Engineering, Konkuk University, Seoul 143-701, South Korea

E-mail:,

Here, we developed a high-throughput MALDI-MS based quantitative targeted glycomics (HT MALDIQTaG) method for analyzing total N-glycans. Although the chemical derivatization processes (i.e., neutralization of sialic acid and incorporation of a positively-charged moiety) were performed in a 96-well with built-in 10 kDa MWCO membrane filters, the quantitative linearity was still quite good (R2 > 0.99) between varying amounts of the target glycoprotein and the MALDI peak intensities. In addition, we validated the relative quantitative reproducibilities in different well positions in a 96-well plate. As a proof-of-concept, the proposed HT MALDI-QTaG method was successfully used to analyze bovine fetuin, human serum and Enbrel1.

Keywords:High-throughput analysis;MALDI-MS;N-glycan;UPLC-FLR;Biopharmaceuticals

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[1] Marth JD, Grewal PK, Nat. Rev. Immunol., 8, 874 (2008)

[2] Arnold JN, Wormald MR, Sim RB, Rudd PM, Dwek RA, Annu. Rev. Immunol., 25, 21 (2007)

[3] Galvanin F, Barolo M, Padrini R, Casonato A, Bezzo F, AIChE J., 60(5), 1718 (2014)

[4] Dennis JW, Granovsky M, Warren CE, Bioessays, 21, 412 (1999)

[5] Ohtsubo K, Marth JD, Cell, 126, 855 (2006)

[6] Durand G, Seta N, Clin. Chem., 46, 795 (2000)

[7] Jensen LJ, Gupta R, Blom N, Devos D, Tamames J, Kesmir C, Nielsen H, Staerfeldt HH, Rapacki K, Workman C, Andersen CA, Knudsen S, Krogh A, Valencia A, Brunak S, J. Mol. Biol., 319, 1257 (2002)

[8] Kukuruzinska MA, Lennon K, Crit. Rev. Oral. Biol. Med., 9, 415 (1998)

[9] Durocher Y, Butler M, Curr. Opin. Biotechnol., 20, 700 (2009)

[10] Jenkins N, Cytotechnology, 53, 121 (2007)

[11] Gomord V, Sourrouille C, Fitchette AC, Bardor M, Pagny S, Lerouge P, Faye L, Plant Biotechnol. J., 2, 83 (2004)

[12] Gervais A, Hammel YA, Pelloux S, Lepage P, Baer G, Carte N, Sorokine O, Strub JM, Koerner R, Leize E, Van Dorsselaer A, Glycobiology, 13, 179 (2003)

[13] Planinc AD, Dejaegher B, Heyden YV, Vianene J, Van Praet S, Rappez F, Van Antwerpen P, Delporte C, Eur. J. Hosp. Pharm., (in press). (2016)

[14] Barroso B, Dijkstra R, Geerts M, Lagerwerf F, van Veelen P, de Ru A, Rapid Commun. Mass Spectrom., 16, 1320 (2002)

[15] Huang L, Biolsi S, Bales KR, Kuchibhotla U, Anal. Biochem., 349, 197 (2006)

[16] Takegawa Y, Deguchi K, Ito S, Yoshioka S, Sano A, Yoshinari K, Kobayashi K, Nakagawa H, Monde K, Nishimura S, Anal. Chem., 76, 7294 (2004)

[17] Royle L, Campbell MP, Radcliffe CM, White DM, Harvey DJ, Abrahams JL, Kim YG, Henry GW, Shadick NA, Weinblatt ME, Lee DM, Rudd PM, Dwek RA, Anal. Biochem., 376, 1 (2008)

[18] Ahn J, Bones J, Yu YQ, Rudd PM, Gilar M, J. Chromatogr. B Anal. Technol. Biomed. Life Sci., 878, 403 (2010)

[19] Bones J, Mittermayr S, O’Donoghue N, Guttman A, Rudd PM, Anal. Chem., 82, 10208 (2010)

[20] Stockmann H, Adamczyk B, Hayes J, Rudd PM, Anal. Chem., 85, 8841 (2013)

[21] Dotz V, Haselberg R, Shubhakar A, Kozak PR, Falck D, Rombouts Y, Reusch D, Somsen GW, Fernandes DL, Wuhrer M, Trends Anal. Chem., 73, 1 (2015)

[22] Thaysen-Andersen M, Mysling S, Hojrup P, Anal. Chem., 81, 3933 (2009)

[23] North SJ, Hitchen PG, Haslam SM, Dell A, Curr. Opin. Struct. Biol., 19, 498 (2009)

[24] Kang P, Mechref Y, Klouckova I, Novotny MV, Rapid Commun. Mass Spectrom., 19, 3421 (2005)

[25] Kang P, Mechref Y, Novotny MV, Rapid Commun. Mass. Spectrom., 22, 721 (2008)

[26] Mechref Y, Kang P, Novotny MV, Methods Mol. Biol., 534, 53 (2009)

[27] Gil GC, Kim YG, Kim BG, Anal. Biochem., 379, 45 (2008)

[28] Jang KS, Kim YG, Gil GC, Park SH, Kim BG, Anal. Biochem., 386, 228 (2009)

[29] Sekiya S, Wada Y, Tanaka K, Anal. Chem., 77, 4962 (2005)

[30] Gil GC, Iliff B, Cerny R, Velander WH, Van Cott KE, Anal. Chem., 82, 6613 (2010)

[31] Kim KJ, Kim YW, Hwang CH, Park HG, Yang YH, Koo M, Kim YG, Biotechnol. Lett., 37(10), 2019 (2015)

[32] Shinohara Y, Furukawa J, Niikura K, Miura N, Nishimura S, Anal. Chem., 76, 6989 (2004)

[33] Prien JM, Prater BD, Qin Q, Cockrill SL, Anal. Chem., 82, 1498 (2010)

[34] Alvarez-Manilla G, Warren NL, Abney T, Atwood J 3rd, Azadi P, York WS, Pierce M, Orlando R, Glycobiology, 17, 677 (2007)

[35] Kang P, Mechref Y, Kyselova Z, Goetz JA, Novotny MV, Anal. Chem., 79, 6064 (2007)

[36] Kim KJ, Kim YW, Kim YG, Park HM, Jin JM, Kim YH, Yang YH, Lee JK, Chung J, Lee SG, Saghatelian A, Biotechnol. Prog., 31(3), 840 (2015)

[37] Jeong HJ, Kim YG, Yang YH, Kim BG, Anal. Chem., 84, 3453 (2012)

[38] DiPaola M, Li J, Stephens E, J. Bioanal. Biomed., 5, 180 (2013)

[39] Houel S, Hilliard M, Yu YQ, McLoughlin N, Martin SM, Rudd PM, Williams JP, Chen W, Anal. Chem., 86, 576 (2014)