Surface plasmon resonance analysis of complex formation of therapeutic recombinant lysosomal enzymes with domain 9 of human cation-independent mannose 6-phosphate receptor

Molecular Genetics and Metabolism Reports

Hitoshi Sakuraba¹  Takahiro Tsukimura²  Minori Kanzaki²  Tadayasu Togawa²  Yasunori Chiba³ 

[1] Department of Clinical Genetics, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan;Department of Functional Bioanalysis, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan;Glycoscience and Glycotechnology Research Group, Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology, Center 5, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan;

关键词: Lysosomal storage disease;    Lysosomal enzyme;    Cation-independent mannose 6-phosphate receptor;    Enzyme uptake;    Complex formation;    Surface plasmon resonance;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown