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Development of diagnostic probes for mucopolysaccharidosis based on saccharide primer method

Research Project

Project/Area Number 17K19208
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Biomolecular chemistry and related fields
Research InstitutionKeio University

Principal Investigator

Sato Toshinori  慶應義塾大学, 理工学部(矢上), 教授 (00162454)

Co-Investigator(Renkei-kenkyūsha) 小野寺 雅史  国立成育医療研究センター, 成育遺伝研究部, 部長 (10334062)
中島 英規  国立成育医療研究センター, マススクリーニング研究室, 研究員 (30450620)
Project Period (FY) 2017-06-30 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords糖鎖プライマー法 / ムコ多糖症 / グリコサミノグリカン / 質量分析装置 / 糖鎖ライブラリー / 早期診断 / 診断薬 / 糖鎖プライマー / LC-MS / 新生児マススクリーニング / 糖鎖 / 診断 / 質量分析
Outline of Final Research Achievements

Mucopolysaccharidosis (MPS) is one of the congenital lysosomal diseases. In this study, in order to realize early diagnosis of MPS, we have prepared a saccharide library to be a diagnostic probe that can be used in newborn screening.
For preparation of a saccharide library, saccharide primer Xyl-Ser-C12, which is a precursor of a glycan biosynthesis pathway, was used. The saccharide primer was added to the cell culture medium of normal human skin fibroblasts, and the structure of the obtained saccharide library was analyzed by LC-MS. In order to search MPS diagnostic substrate compounds from the obtained saccharide library, sequence analysis was performed using glycolytic enzymes. As a result, sugar chains that can be used as diagnostic substrates for MPS type I and type II were obtained.

Academic Significance and Societal Importance of the Research Achievements

ムコ多糖症とは先天性代謝疾患である。ムコ多糖症患者は生まれつきライソゾームに存在するグリコサミノグリカン (GAG) を分解する酵素が欠損しており、その結果、ムコ多糖が体内に蓄積し、臓器の肥大化や骨の変形など様々な障害を引き起こす。ムコ多糖症は進行性疾患のため、早期診断により、早期治療が必要である。そこで、新生児マススクリーニングにおいてムコ多糖症の診断を可能にする基質を開発することで、早期診断と早期治療が可能となる。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (9 results)

All 2019 2018 2017

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (6 results) (of which Int'l Joint Research: 1 results) Book (1 results)

  • [Journal Article] Comparative Quantification Method for Glycosylated Products Elongated on β-Xylosides Using a Stable Isotope-Labeled Saccharide Primer2018

    • Author(s)
      Yuya Otsuka, Toshinori Sato
    • Journal Title

      Anal. Chem.

      Volume: 90 Issue: 8 Pages: 5201-5208

    • DOI

      10.1021/acs.analchem.7b05438

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Saccharide primers comprising xylosyl-serine primed phosphorylated oligosaccharides act as intermediates in glycosaminoglycan biosynthesis2017

    • Author(s)
      Yuya Otsuka, Toshinori Sato
    • Journal Title

      ACS Omega

      Volume: 2 Issue: 7 Pages: 3110-3122

    • DOI

      10.1021/acsomega.7b00073

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 糖鎖プライマー法を用いたムコ多糖症の診断基質の開発2019

    • Author(s)
      八木柚香、渡辺摩周、松林慶一、中島英規、小野寺雅史、佐藤智典
    • Organizer
      第68回高分子学会年次大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 糖鎖プライマー法によるがん細胞に発現するムチン型O-グリカンの多様性 / アミノ酸残基選択性の解析2018

    • Author(s)
      長井 香、佐々木克昌、佐倉隆馬、佐藤智典
    • Organizer
      GlycoTOKYO
    • Related Report
      2018 Annual Research Report
  • [Presentation] 糖鎖プライマー法によるがん細胞のラクト/ネオラクト型糖鎖発現プロファイル解析と細胞運動能との相関解析2018

    • Author(s)
      城代航、佐々木克昌、佐藤智典
    • Organizer
      GlycoTOKYO
    • Related Report
      2018 Annual Research Report
  • [Presentation] 糖鎖プライマー法を用いたがん細胞で発現するムチン型O-グリカンの多様性及びアミノ酸及びアミノ酸残基選択性の解析2018

    • Author(s)
      長井香、佐々木克昌、佐倉隆馬、佐藤 智典
    • Organizer
      第37回糖質学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ムコ多糖症の新生児マススクリーニングに向けたGAG型オリゴ糖基質の開発2018

    • Author(s)
      渡辺 摩周、松林 慶一、小野寺 雅史、市田 悠、中島 英規、佐藤 智典
    • Organizer
      日本化学会第98春季年会
    • Related Report
      2017 Research-status Report
  • [Presentation] Structure analysis of glycosaminoglycan intermediate oligosaccharides elongated on -xylosides2017

    • Author(s)
      Yuya Otsuka, Toshinori Sato
    • Organizer
      65th Conference on Mass Spectrometry and Allied Topics
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Book] 中分子創薬に資するペプチド・核酸・糖鎖の合成技術2018

    • Author(s)
      佐藤 智典
    • Total Pages
      317
    • Publisher
      CMC出版
    • Related Report
      2017 Research-status Report

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Published: 2017-07-21   Modified: 2020-03-30  

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