Abstract：
:In this study we developed an efficient method to prepare glycoengineered β-N-acetylhexosaminidase containing multiple mannose-6-phosphates (M6Ps) by combining genetic code expansion with bioorthogonal ligation techniques. We found that multiple M6P-conjugated enzymes were produced with a high efficiency by using combined techniques. Importantly, glycoengineered enzymes entered lysosomes of patient-derived primary cells, which lack endogenous lysosomal β-N-acetylhexosaminidase, more readily than commercialized human β-hexosaminidase. Moreover, glycoengineered enzymes successfully removed GM2-ganglioside stored in lysosomes of diseased cells, indicating that its activity is restored in diseased cells. We also synthesized and applied a lysosome-targeting fluorogenic substrate to monitor endogenous and supplemental glycoengineered β-N-acetylhexosaminidase activities in lysosomes. The results of this study indicate that the present strategy, which relies on genetic code expansion and bioorthogonal ligation techniques, is highly attractive to generate multi-M6P-containing lysosomal enzymes that can be used to study lysosomal storage disorders associated with lysosomal enzyme deficiencies.
journal_name
Cell Chem Bioljournal_title
Cell chemical biologyauthors
Hyun JY,Kim S,Lee HS,Shin Idoi
10.1016/j.chembiol.2018.07.011subject
Has Abstractpub_date
2018-10-18 00:00:00pages
1255-1267.e8issue
10eissn
2451-9456issn
2451-9448pii
S2451-9456(18)30263-0journal_volume
25pub_type
杂志文章abstract：:In this issue of Cell Chemical Biology, Shah et al. (2019) report an in vitro, high-throughput assay that predicts the ability of compounds to suppress peroxidation of phospholipids. This approach provides a way to design and optimize targeted antioxidants that suppress specific oxidative event in cells, potentially o...
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journal_title：Cell chemical biology
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journal_title：Cell chemical biology
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journal_title：Cell chemical biology
pub_type： 杂志文章
doi：10.1016/j.chembiol.2018.06.007
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journal_title：Cell chemical biology
pub_type： 杂志文章
doi：10.1016/j.chembiol.2017.09.007
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