Structure and function of oligosaccharide of glycoprotein : Approach by recombinant technology and organic synthesis.
糖蛋白寡糖的结构和功能:重组技术和有机合成方法。
基本信息
- 批准号:07406016
- 负责人:
- 金额:$ 1.6万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (A)
- 财政年份:1995
- 资助国家:日本
- 起止时间:1995 至 1996
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Oligosaccharides modify the structure, dynamics and physical properties of the proteins to which they are covalently bound through nitrogen to aspargine or oxygen to serine or threonine. After the breakthrough of cDNA cloning, the primary structure is deduced from the sequence of nucleotides in the cDNA encoding the protein. From the derived sequence, certain properties of the protein can be predicted including potential glycosilation sites for N-linked glycans. Oligosaccharide structure and function, however, can not be deduced from the nucleotide sequence. In this research project, we have studied on the biological activity of several glycoproteins including Leukemia lnhibitory Factor (LIF), Placental Lactogen (PL) and Chorionic Gonadotropin (CG) using techniques including molecular cloning, site-directed mutagenesis and organic synthesis of oligosaccharides. We have cloned the cDNA which encodes LIF in the rat. LIF is a member of a cytokine superfamily and has diverse functions in the various tissues and cells. Of seven possible N-glycosilation sites, six sites are glycosilated at positions of 9,34,63,73,96 and 116. These oligosaccharides are involved in the biological function when the activity was evaluated in the DA-1a cell proliferation system. PL-lm is a member of the placental prolactin family and has two possible N-glycosilation sites (79 and 128). The mutants of PLs of which substituting the Asn 79 and Asn 128 with Gln showed significant decrease of Nb2 cell proliferation. Equine CG (eCG) is a unique member of gonadotropin, because it possesses both LH and FSH activities. The eCG mutant which lack N-glycan of a-subunit (Asn56) showed complete loss of LH-like activity but showed potent FSH-like activity. eCG has also O-glycans at the C-teminal portion of b-subunit. The mutant which lack O-linked oligosaccharides was also shoed potent FSH like activity. Thus, we demonstrated the biological importance of oligosaccharides in the glycoproteins.
寡聚核苷酸通过氮与精氨酸或氧与丝氨酸或苏氨酸共价结合,从而改变蛋白质的结构、动力学和物理性质。在cDNA克隆的突破之后,从编码蛋白质的cDNA中的核苷酸序列推断出一级结构。从衍生的序列中,可以预测蛋白质的某些性质,包括N-连接聚糖的潜在糖基化位点。然而,不能从核苷酸序列推断寡糖的结构和功能。本课题采用分子克隆、定点突变和寡糖有机合成等技术对白血病抑制因子(LIF)、胎盘催乳素(PL)和绒毛膜促性腺激素(CG)等糖蛋白的生物活性进行了研究。我们克隆了大鼠LIF的cDNA。LIF是细胞因子超家族的成员,在各种组织和细胞中具有不同的功能。在7个可能的N-糖基化位点中,6个位点在9、34、63、73、96和116位发生糖基化。当在DA-1a细胞增殖系统中评价活性时,这些寡糖参与生物学功能。PL-1 m是胎盘催乳素家族的成员,具有两个可能的N-糖基化位点(79和128)。Asn 79和Asn 128被Gln取代的PLs突变体对Nb 2细胞的增殖有明显的抑制作用。马CG(eCG)是促性腺激素的独特成员,因为它同时具有LH和FSH活性。缺乏α-亚基N-聚糖的eCG突变体(Asn 56)显示LH样活性的完全丧失,但显示有效的FSH样活性。eCG在b-亚基的C-末端部分也具有O-聚糖。缺乏O-连接寡糖的突变体也显示出有效的FSH样活性。因此,我们证明了糖蛋白中低聚糖的生物学重要性。
项目成果
期刊论文数量(22)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
K.W.Neumann, J.Tamura and T.Ogawa: "A stereocontrolled synthetic approach to giycopeptides corresponding to the carbohydrate-protein linkage region of cell-surface proteoglycans." Bioorg. Med. Chem.3. 1637-1650 (1995)
K.W.Neumann、J.Tamura 和 T.Okawa:“一种立体控制的糖肽合成方法,对应于细胞表面蛋白聚糖的碳水化合物-蛋白质连接区域。”
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Yoshiaki Nakahara et al.: "Solid-phase synthesis of an O-linked glycopeptide based on a benzyl-protected glycan approach" Carbohydr.Res.292. 71-81 (1996)
Yoshiaki Nakahara 等人:“基于苄基保护聚糖方法的 O-连接糖肽的固相合成”CarboHydr.Res.292。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
I.Matsuo et al.: "Synthesis of glycopeptide carrying a N-linked core pentasaccharide." Bioorganic & Medicinal Chemistry. 3. 1455-1463 (1995)
I.Matsuo 等人:“携带 N-连接核心五糖的糖肽的合成。”
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
I.Matsuo, Y.Nakahara, Y.Ito, T.Nukada, Y.Nakahara, and T.Ogawa: "Synthesis of a glycopeptide carrying a N-linked core pentasaccharide." Bioorg. Med. Chem.3. 1455-1463 (1995)
I.Matsuo、Y.Nakahara、Y.Ito、T.Nukada、Y.Nakahara 和 T.Okawa:“携带 N 连接核心五糖的糖肽的合成”。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
W.M.Macindoe et al.: "Stereoselective synthesis of a blood group A type glycopaptide present in human blood mucin." Carbohydrate Res.269. 227-257 (1995)
W.M.Macindoe 等人:“人血液粘蛋白中存在的 A 型血型糖肽的立体选择性合成。”
- DOI:
- 发表时间:
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- 影响因子:0
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OGAWA Tomoya其他文献
The Influential Factors to Lower Attitude Pupil's Learning Behavior toward Physical Education Class
低态度小学生体育课学习行为的影响因素
- DOI:
- 发表时间:
2003 - 期刊:
- 影响因子:0
- 作者:
OTOMO Satoshi;OGAWA Tomoya - 通讯作者:
OGAWA Tomoya
OGAWA Tomoya的其他文献
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{{ truncateString('OGAWA Tomoya', 18)}}的其他基金
Effects of Alkalizing Agents (THAM) on Ischemic Brain Injuries
碱化剂 (THAM) 对缺血性脑损伤的影响
- 批准号:
11671369 - 财政年份:1999
- 资助金额:
$ 1.6万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Tomographic detection of micro-defects in semi-conductions due to light scattering and photoluminescence imaging
由于光散射和光致发光成像而导致的半导体微缺陷的断层扫描检测
- 批准号:
10450011 - 财政年份:1998
- 资助金额:
$ 1.6万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Study on generation of glycoprotein by recombinant technology.
重组技术产生糖蛋白的研究。
- 批准号:
06556058 - 财政年份:1994
- 资助金额:
$ 1.6万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
A new fringe method for characterization of ROUGHNESS of inner layrs in semiconductor crystals and dielectric thin layrs
表征半导体晶体和电介质薄层内层粗糙度的新条纹方法
- 批准号:
04555006 - 财政年份:1992
- 资助金额:
$ 1.6万 - 项目类别:
Grant-in-Aid for Developmental Scientific Research (B)
Characterization of and detection of defects in semiconductor crystals by infrared light scattering tomography
通过红外光散射断层扫描表征和检测半导体晶体中的缺陷
- 批准号:
04402018 - 财政年份:1992
- 资助金额:
$ 1.6万 - 项目类别:
Grant-in-Aid for General Scientific Research (A)
Placental function and development of fetal nervous system.
胎盘功能和胎儿神经系统的发育。
- 批准号:
04304024 - 财政年份:1992
- 资助金额:
$ 1.6万 - 项目类别:
Grant-in-Aid for Co-operative Research (A)
Study on the biological roles of oligosaccharides : approach by analysis and organic synthesis of oligosaccharides.
低聚糖的生物学作用研究:低聚糖的分析和有机合成方法。
- 批准号:
03404012 - 财政年份:1991
- 资助金额:
$ 1.6万 - 项目类别:
Grant-in-Aid for General Scientific Research (A)
Characterization of Epitaxial Layers and Ion-Implanted Surfaces on Semiconductor Wafers by Scattering of Light and Optical Surface Waves
通过光和光学表面波散射表征半导体晶圆上的外延层和离子注入表面
- 批准号:
63460059 - 财政年份:1988
- 资助金额:
$ 1.6万 - 项目类别:
Grant-in-Aid for General Scientific Research (B)
Design and Prototype Construction of Infrared Resonance Scattering Tomography
红外共振散射断层扫描的设计与样机构建
- 批准号:
61850006 - 财政年份:1986
- 资助金额:
$ 1.6万 - 项目类别:
Grant-in-Aid for Developmental Scientific Research
Growth History of III-V Compound Crystals by IR Light Scattering Tomograpyhy
红外光散射断层扫描 III-V 族化合物晶体的生长历史
- 批准号:
61460238 - 财政年份:1986
- 资助金额:
$ 1.6万 - 项目类别:
Grant-in-Aid for General Scientific Research (B)
相似海外基金
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