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  • 02월 28일 17시 이후 : 초록수정 불가능, 일정확인 및 검색만 가능

제123회 대한화학회 학술발표회, 총회 및 기기전시회 안내 Activity of glycoengineered β-N-Acetylhexosaminidases with multiple mannose-6-phosphates in lysosomes

2019년 2월 14일 14시 25분 05초
LIFE.O-4 이곳을 클릭하시면 발표코드에 대한 설명을 보실 수 있습니다.
목 09시 : 45분
Life Chemistry - Oral Presentation of Young Life Chemist
저자 및
Hyun Jiyoung, Injae Shin*
Department of Chemistry, Yonsei University, Korea
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.