Earticle

초록

영어

The genetic deficiency of lysosomal β-N-acetylhexosaminidases leads to incomplete digestion of GM2-ganglioside and thus causes its progressive accumulation in lysosomes. This defect causes the onset of Tay-Sachs and Sandhoff diseases, a class of lysosomal storage disorders (LSDs). To remove GM2-ganglioside accumulated in Tay-Sachs and Sandhoff diseased cells, multiple mannose-6-phosphate (M6P)-appended β -N-acetylhexosaminidases were prepared by click chemistry between multiple M6P-containing N3-peptides and alkynylated enzymes obtained by genetic code expansion. In addition, lysosome-targeting, near-infrared (NIR)-based fluorogenic probes were synthesized and applied for (real-time) monitoring of lysosomal β-N-acetylhexosaminidase activity in cells. It was found that the multiple M6P-appended β-N-acetylhexosaminidase efficiently internalizes cells via M6P receptor-mediated endocytosis and then reaches the lysosome to regain its enzyme activity. Furthermore, the glycoengineered enzyme was able to efficiently cleave GM2-ganglioside in primary diseased cells, indicating the restoration of its activity in cells. The present strategy using the coupled genetic code expansion and biorthogonal ligation techniques is highly attractive to construct multiple M6P-containing enzymes which can be used to study LSDs.

저자

• Ji Young Hyun [ Center for Biofunctional Molecules, Department of Chemistry, Yonsei University, Seoul 03722, Korea ]
• Injea Shin [ Center for Biofunctional Molecules, Department of Chemistry, Yonsei University, Seoul 03722, Korea ]

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간행물

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• 간행물명

  한국당과학회 학술대회

• 간기

  연간

• 수록기간

  2006~2022

• 십진분류

  KDC 517 DDC 614