期刊
MOLECULAR GENETICS AND METABOLISM REPORTS
卷 25, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ymgmr.2020.100639
关键词
Lysosomal storage disease; Lysosomal enzyme; Cation-independent mannose 6-phosphate receptor; Enzyme uptake; Complex formation; Surface plasmon resonance
资金
- Sumitomo Dainippon Pharma Co., Ltd.
- Sanofi Japan Co.
- JSPS KAKENHI [JP18K15071]
The efficacy of enzyme replacement therapy (ERT) for lysosomal storage diseases (LSDs) possibly depends on the cellular uptake of recombinant lysosomal enzymes (LEs), and it is known that cation-independent mannose 6-phosphate receptor (CI-M6PR) on the cell membrane is predominantly involved in the endocytosis of many LEs. To examine the biomolecular interaction between therapeutic LEs and CI-M6PR, we biophysically analyzed the complex formation of four LEs available with domain 9 of human CI-M6PR, a binding site of the receptor, by means of surface plasmon resonance (SPR) biosensor assays. The results revealed that the affinity of the LEs for domain 9 of the receptor increased in the following order: laronidase, agalsidase beta, idursulfase, and alglucosidase alfa; and the high affinity of laronidase for domain 9 of CI-M6PR was due to fast complex formation rather than slow dissociation of the complex. The affinity of the enzymes for domain 9 of CI-M6PR almost coincided with their cellular uptake. The SPR biosensor assay is sensitive and provides important information for the development of effective therapeutic LEs for LSDs.
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