TY - JOUR
T1 - Surface plasmon resonance analysis of complex formation of therapeutic recombinant lysosomal enzymes with domain 9 of human cation-independent mannose 6-phosphate receptor
AU - Kanzaki, Minori
AU - Tsukimura, Takahiro
AU - Chiba, Yasunori
AU - Sakuraba, Hitoshi
AU - Togawa, Tadayasu
N1 - Publisher Copyright:
© 2020 The Authors
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
KW - Cation-independent mannose 6-phosphate receptor
KW - Complex formation
KW - Enzyme uptake
KW - Lysosomal enzyme
KW - Lysosomal storage disease
KW - Surface plasmon resonance
UR - https://www.scopus.com/pages/publications/85089659455
U2 - 10.1016/j.ymgmr.2020.100639
DO - 10.1016/j.ymgmr.2020.100639
M3 - Article
AN - SCOPUS:85089659455
SN - 2214-4269
VL - 25
JO - Molecular Genetics and Metabolism Reports
JF - Molecular Genetics and Metabolism Reports
M1 - 100639
ER -