Glycoconjugate Journal

, Volume 31, Issue 4, pp 309–315 | Cite as

A biochemical and physicochemical comparison of two recombinant enzymes used for enzyme replacement therapies of hunter syndrome

  • Yo Kyung Chung
  • Young Bae Sohn
  • Jong Mun Sohn
  • Jieun Lee
  • Mi Sun Chang
  • Younghee Kwun
  • Chi Hwa Kim
  • Jin Young Lee
  • Yeon Joo Yook
  • Ah-Ra Ko
  • Dong-Kyu Jin


Mucopolysaccharidosis II (MPS II, Hunter syndrome; OMIM 309900) is an X-linked lysosomal storage disease caused by a deficiency in the enzyme iduronate-2-sulfatase (IDS), leading to accumulation of glycosaminoglycans (GAGs). For enzyme replacement therapy (ERT) of Hunter syndrome, two recombinant enzymes, idursulfase (Elaprase®, Shire Human Genetic Therapies, Lexington, MA) and idursulfase beta (Hunterase®, Green Cross Corporation, Yongin, Korea), are currently available in Korea. To compare the biochemical and physicochemical differences between idursulfase and idursulfase beta, we examined the formylglycine (FGly) content, specific enzyme activity, mannose-6-phosphate (M6P) content, sialic acid content, and in vitro cell uptake activity of normal human fibroblasts of these two enzymes.

The FGly content, which determines the enzyme activity, of idursulfase beta was significantly higher than that of idursulfase (79.4 ± 0.9 vs. 68.1 ± 2.2 %, P < 0.001). In accordance with the FGly content, the specific enzyme activity of idursulfase beta was significantly higher than that of idursulfase (42.6 ± 1.1 vs. 27.8 ± 0.9 nmol/min/μg protein, P < 0.001). The levels of M6P and sialic acid were not significantly different (2.4 ± 0.1 vs 2.4 ± 0.3 mol/mol protein for M6P and 12.3 ± 0.7 vs. 12.4 ± 0.4 mol/mol protein for sialic acid). However, the cellular uptake activity of the normal human fibroblasts in vitro showed a significant difference (Kuptake, 5.09 ± 0.96 vs. 6.50 ± 1.28 nM protein, P = 0.017).

In conclusion, idursulfase beta exhibited significantly higher specific enzyme activity than idursulfase, resulting from higher FGly content. These biochemical differences may be partly attributed to clinical efficacy. However, long-term clinical evaluations of Hunter syndrome patients treated with these two enzymes will be needed to demonstrate the clinical implications of significant difference of the enzyme activity and the FGly content.


Hunter syndrome MPS II Iduronate-2-sulfatase Formylglycine Mannose-6-phosphate Enzyme replacement therapy 



This study was sponsored by Green Cross Corp. (Yongin, Korea). This study was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A101779). We thank Myeong-suk Moon and Jun-mo Bae for helpful supporting on specific enzyme activity assay and in vitro cell uptake assay.

All of the authors have nothing to disclose.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Yo Kyung Chung
    • 1
    • 2
  • Young Bae Sohn
    • 3
  • Jong Mun Sohn
    • 2
  • Jieun Lee
    • 4
  • Mi Sun Chang
    • 4
  • Younghee Kwun
    • 4
  • Chi Hwa Kim
    • 5
  • Jin Young Lee
    • 6
  • Yeon Joo Yook
    • 6
  • Ah-Ra Ko
    • 6
  • Dong-Kyu Jin
    • 4
  1. 1.Department of Molecular Science and TechnologyAjou UniversitySuwonSouth Korea
  2. 2.Bioprocess EngineeringCentral Research Center, Green Cross CorporationYonginSouth Korea
  3. 3.Department of Medical GeneticsAjou University School of MedicineSuwonSouth Korea
  4. 4.Department of Pediatrics, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulSouth Korea
  5. 5.Rare Diesase TeamMogam Biotechnology Research InstituteYonginSouth Korea
  6. 6.Clinical Research CenterSamsung Biomedical Research InstituteSeoulSouth Korea

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