Synthesis of complex-type glycan containing LacdiNAc structure and its application to the glycoprotein synthesis

含LacdiNAc结构的复合型聚糖的合成及其在糖蛋白合成中的应用

• 批准号: 23380065
• 负责人: HOJO Hironobu
• 金额: $ 7.24万
• 依托单位: Osaka University (2013)Tokai University (2011-2012)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23380065/
• 关键词: 糖タンパク質; グライコデリン; 糖ペプチドチオエステル; セグメント縮合法; LacdiNAc; glycodelin; ペプチドチオエステル; 化学合成

Glycodelin A (GdA), a glycoprotein of 162 amino acid residues, has unusual carbohydrate structures composed of GalNAc-GlcNAc (LacdiNAc), and is engaged in important biological processes, such as fertilization. To promote the functional analysis of GdA as well as LacdiNAc-containing glycan, an access to GdA having homogeneous glycan is required. In this research, the efficient synthetic route of GdA having homogeneous glycan was examined. The synthesis of LacdiNAc-containing carbohydrate was realized by our benzyl-protection strategy. The polypeptide composed of the entire GdA sequence carrying GlcNAcs was then assembled by the native chemical ligation method combined with our N-alklycysteine-assisted thioesterification method. After folding, GdA having GlcNAcs was reacted with LacdiNAc sugar by glycosynthase to derivatize into GdA having LacdiNAc sugar.

Glycodelin A（GdA）是一种由162个氨基酸残基组成的糖蛋白，具有由GalNAc-GlcNAc（LacdiNAc）组成的不寻常的碳水化合物结构，并且参与重要的生物学过程，例如受精。为了促进GdA以及含LacdiNAc聚糖的功能分析，需要获得具有同质聚糖的GdA。在本研究中，GdA具有均匀的聚糖的有效合成路线进行了检查。通过苄基保护策略实现了含LacdiNAc的碳水化合物的合成。然后通过天然化学连接方法结合我们的N-烷基半胱氨酸辅助硫代酯化方法组装由携带GlcNAc的整个GdA序列组成的多肽。折叠后，通过糖合酶使具有GlcNAc的GdA与LacdiNAc糖反应以衍生为具有LacdiNAc糖的GdA。

项目成果

Synthesis of TIM-3 Ig-like domain carrying a complex-type carbohydrate

携带复合型碳水化合物的 TIM-3 Ig 样结构域的合成

• 发表时间: 2013
• 作者: Asahina;Y.;Kamitori;S.;Hojo;H
• 通讯作者: H

セグメント縮合法を用いた糖タンパク質Tim-3 IgV ドメインの合成研究

糖蛋白Tim-3 IgV结构域的片段缩合法合成研究

• 发表时间: 2012
• 作者: 朝比奈雄也;片山秀和;神鳥成弘;北條裕信
• 通讯作者: 北條裕信

Efficient synthesis of Fmoc-aminoacyl-N-ethylcysteine, a key device for peptide thioester preparation

肽硫酯制备关键装置Fmoc-氨酰基-N-乙基半胱氨酸的高效合成

• 发表时间: 2011
• 作者: Asahina;Y.;Kobayashi;H.;Ubagai;R.;Katayama;H.;Nakahara;Y.;Ito;Y.;Nakahara;Y.;Hojo;H
• 通讯作者: H

Study of the Substituent effect on the N-alkylcysteine-assisted thioesterification

取代基对N-烷基半胱氨酸辅助硫酯化反应影响的研究

• 发表时间: 2013
• 作者: Asahina;Y.;Nabeshima;K.;Hojo;H
• 通讯作者: H

Facile synthesis of gelatinase biosynthesisactivating pheromone (GBAP), a bacterical peptide lactone

轻松合成明胶酶生物合成激活信息素 (GBAP)，一种细菌肽内酯

• 发表时间: 2013
• 作者: Katayama;H.;Nagata;K.;Tanokura;M.;Nakayama;J.;Sonomoto;K.;Hojo;H
• 通讯作者: H