A biochemical and physicochemical comparison of two recombinant enzymes used for enzyme replacement therapies of hunter syndrome
| Autor: | Dong-Kyu Jin, Young Bae Sohn, Yeon Joo Yook, Jieun Lee, Yo Kyung Chung, Jong Mun Sohn, Younghee Kwun, Chi Hwa Kim, Ah-Ra Ko, Mi Sun Chang, Jin Young Lee |
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| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
Idursulfase Recombinant Fusion Proteins Glycine CHO Cells Iduronate Sulfatase Biochemistry chemistry.chemical_compound Cricetulus Internal medicine Cricetinae medicine Lysosomal storage disease Animals Humans Enzyme Replacement Therapy Molecular Biology Mucopolysaccharidosis II Alanine Mannosephosphates biology Chemistry Iduronate-2-sulfatase Hunter syndrome Cell Biology Enzyme replacement therapy Fibroblasts medicine.disease Enzyme assay N-Acetylneuraminic Acid Sialic acid Endocrinology biology.protein N-Acetylneuraminic acid medicine.drug |
| Zdroj: | Glycoconjugate journal. 31(4) |
| ISSN: | 1573-4986 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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