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Generation of Biobetter therapeutic enzymes with improved lysosomal targeting capabilities
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- 발행기관
- 한국당과학회 바로가기
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- 간행물
- 한국당과학회 학술대회 바로가기
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- 통권
- 2020 한국당과학회 연례학술대회(온라인) (2021.01)바로가기
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- 페이지
- pp.28-29
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- 저자
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- 언어
- 영어(ENG)
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- URL
- https://www.earticle.net/Article/A390434
※ 원문제공기관과의 협약기간이 종료되어 열람이 제한될 수 있습니다.
원문정보
초록
- 영어
- Lysosomal storage diseases (LSDs), a group of inherent diseases, are caused by hydrolase deficiency, which results in the accumulation of undigested metabolites in the lysosome. For the treatment of LSDs, enzyme replacement therapies with recombinant enzymes have been used successfully. Most of the therapeutic enzymes, except for the ones for Gaucher disease, require mannose-6-phosphate (M6P) glycans that are recognized by mannose-6-phosphate receptors on the plasma membrane for cellular uptake and targeting to lysosomes. Therefore, M-6-P content is a key factor for efficient MPR binding and lysosomal delivery, which is essential for clearance of the accumulated molecules. Several glyco-engineering strategies for increasing M6P glycan content have been designed to produce “Biobetter” enzymes for LSDs [1]. We constructed the glyco-engineered yeast harboring high content of mannosylphosphorylated glycans, which can be converted M6P glycans by uncapping of the outer mannose residue. The short glycopeptides containing M6P glycans (M6PgPs) were prepared from cell wall mannoproteins of the glyco-engineered yeast by using hot-citrate buffer extraction and pronase digestion. The purified M6PgPs were successfully conjugated to a therapeutic enzyme, recombinant acid a-glucosidase (rGAA) used for treatment of Pompe disease, by two-step reactions using two hetero-bifunctional corsslinkers. The M6PgP-conjugated rGAA had 18-fold higher content of M6P glycan than rGAA and displayed greatly increased its uptake by Pompe disease patient fibroblasts [2]. For the first time, a strategy for in vitro mannosyl-phosphorylation of high-mannose type N-glycans has been established employing a recombinant Mnn14 protein (rM14) derived from Saccharomyces cerevisiae. In vitro reaction using rM14 mannosyl-phosphorylated the glycans on rhGAA, which can be converted to have high M6P glycans contents. It will promise the generation of “Biobetter” therapeutic enzymes with improved lysosomal targeting capability.
저자
간행물 정보
발행기관
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- 발행기관명
- 한국당과학회 [Korean Society for Glycoscience]
- 설립연도
- 2006
- 분야
- 의약학>약학
- 소개
- 본 학회는 화학, 생화학, 분자생물학, 미생물학, 식품공학, 의학, 약학, 유전공학 및 생물공학, 환경 및 기타 공업 등 전 분야의 탄수화물관련 이론과 기술을 연구 발전시키고 산학협동을 통해 이를 보급하여 국내 관련 산업의 발전 및 국민생활의 과학화에 기여하고자 하며, 이러한 목표와 비젼의 실현을 위해 회원들이 적극적인 참여와 활동을 전개하고자 한다.
간행물
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- 간행물명
- 한국당과학회 학술대회
- 간기
- 연간
- 수록기간
- 2006~2022
- 십진분류
- KDC 517 DDC 614
이 권호 내 다른 논문 / 한국당과학회 학술대회 2020 한국당과학회 연례학술대회(온라인)
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