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The Relationship between the Branch-Forming Glycosyltransferases and Cell Surface Sugar Chain Structures

机译:分支形成糖基转移酶与细胞表面糖链结构之间的关系

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摘要

Many recombinant proteins developed or under development for clinical use are glycoproteins,and trials aimed at improving their bioactivity or pharmacokinetics in vivo by altering specific glycan structures are ongoing.For Pharmaceuticals of glycoproteins,it is important to characterize and,if possible,control the glycosylation profile.However,the mechanism responsible for the regulation of sugar chain structures found on naturally occurring glycoproteins is still unclear.To clarify the relationship between glycosyltransferases and sugar chain branch structure,we estimated six glycosyltransferases' activities (N-acetylglucosaminyltransferase (GlcNAcTase)-I,-II,-III,-IV,-V,and beta-l,4-galactosyltransferase (GalT)) which control the branch formation on asparagine (Asn)-linked sugar chains in 18 human cancer cell lines derived from several tissues.To visualize the balance of glycosyltransferase activity associated with each cell line,we expressed the relative glycosyltransferase activity in comparison to the average activity among the cell lines.These cell lines were classified into five groups according to their relative glycosyltransferase balance and were termed GlcNAcTase-I/-II,GlcNAcTase-III,GlcNAcTase-IV,GlcNAcTase-V,and GalT.We also characterized the structures of Asn-linked sugar chains on the cell surface of representative cell lines of each group.The branching structure of cell surface sugar chains roughly corresponded to the glycosyltransferase balance.This finding suggests that,for the sugar chain structure remodeling of glycoproteins,attention should be focused on the glycosyltransferase balance of host cells before introducing exogenous glycosyltransferases or down-regulating the activity of intrinsic glycosyltransferases.
机译:发育或正在开发的许多重组蛋白为临床用途是糖蛋白,并且通过改变特异性聚糖结构来改善体内的生物活性或药代动力学的试验正在进行中。对于糖蛋白的药物来说,重要的是表征和,如果可能的话,控制糖基化无论何种,负责调节在天然存在的糖蛋白上发现的糖链结构的机制仍然不清楚。阐明糖基转移酶和糖链分支结构之间的关系,我们估计了六种糖基转移酶的活性(N-乙酰葡糖氨基氨基转移酶(Glcnactase)-i ,控制来自几种组织的18个人癌细胞系中的芦笋(ASN) - 链接糖链中的分支形成,-II,-III,-V,4-半乳糖基转移酶(GALT))。为了可视化与每种细胞系相关的糖基转移酶活性的平衡,我们表达了相对糖基转移酶活性与细胞系中的平均活动相比。这些细胞系根据其相对糖基转移酶平衡分为五组,并称为GlcNactase-I / -II,GlcNactase-III,Glcnactase-IV,Glcnactase-V和Galt。我们还表征了每组代表性细胞系的细胞表面上ASN连接的糖链的结构。细胞表面糖链的分支结构大致对应于糖基转移酶平衡。本发现表明,对于糖链结构的重塑在引入外源性糖基转移酶或降低内在糖基转移酶的活性之前,应注意糖蛋白的注意力应重点关注宿主细胞的糖基三烷基酶平衡。

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  • 来源
    《Biochemistry》 |2005年第16期|共7页
  • 作者单位

    Biomedical Imaging Research Center University of Fukui 23-3 Shimoaizuki Matsuoka Yoshida Fukui 910-1193 Japan and Central Laboratories for Key Technology KIRIN Brewery Company Limited 1-13-5 Fuku-ura Kanazawa-ku Yokohama 236-0004 Japan;

    Biomedical Imaging Research Center University of Fukui 23-3 Shimoaizuki Matsuoka Yoshida Fukui 910-1193 Japan and Central Laboratories for Key Technology KIRIN Brewery Company Limited 1-13-5 Fuku-ura Kanazawa-ku Yokohama 236-0004 Japan;

    Biomedical Imaging Research Center University of Fukui 23-3 Shimoaizuki Matsuoka Yoshida Fukui 910-1193 Japan and Central Laboratories for Key Technology KIRIN Brewery Company Limited 1-13-5 Fuku-ura Kanazawa-ku Yokohama 236-0004 Japan;

    Biomedical Imaging Research Center University of Fukui 23-3 Shimoaizuki Matsuoka Yoshida Fukui 910-1193 Japan and Central Laboratories for Key Technology KIRIN Brewery Company Limited 1-13-5 Fuku-ura Kanazawa-ku Yokohama 236-0004 Japan;

    Biomedical Imaging Research Center University of Fukui 23-3 Shimoaizuki Matsuoka Yoshida Fukui 910-1193 Japan and Central Laboratories for Key Technology KIRIN Brewery Company Limited 1-13-5 Fuku-ura Kanazawa-ku Yokohama 236-0004 Japan;

    Biomedical Imaging Research Center University of Fukui 23-3 Shimoaizuki Matsuoka Yoshida Fukui 910-1193 Japan and Central Laboratories for Key Technology KIRIN Brewery Company Limited 1-13-5 Fuku-ura Kanazawa-ku Yokohama 236-0004 Japan;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物化学;
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