• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >A chemical-enzymatic method for the synthesis of sialylated oligosaccharides: Synthesis of cytidine monophosphate-sialic acid analogs for use in probing the donor specificity of alpha-2,3- and alpha-2,6-sialyltransferase.
【24h】

A chemical-enzymatic method for the synthesis of sialylated oligosaccharides: Synthesis of cytidine monophosphate-sialic acid analogs for use in probing the donor specificity of alpha-2,3- and alpha-2,6-sialyltransferase.

机译：合成唾液酸化寡糖的化学酶法：胞苷一磷酸-唾液酸类似物的合成，用于探测α-2,3-和α-2,6-唾液酸转移酶的供体特异性。

获取原文
获取原文并翻译 | 示例
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Sialic acids are nine-carbon monosaccharides typically found at the termini of animal glycoconjugates and are known to be important sites for biological recognition. An effective method for the incorporation of sialic acid analogs into oligosaccharides utilizes sialyltransferase enzymes, which regio- and stereoselectively transfer sialic acid from the donor compound, cytidine monophoso- N-acetyl neuraminic acid (CMP-Neu5Ac), onto several lactose- and lactosamine-derived acceptors. Sialyltransferases have been shown to tolerate a variety of acceptor modifications, although less is known about the donor specificity due to the difficulty in synthesizing the requisite CMP-Neu5Ac sugar-donors. Consequently, a chemical synthesis of CMP-Neu5Ac analogs, which is amenable to the incorporation of derivatized sialic acids, is a focus of this work.;A key step in the synthesis of the CMP-Neu5Ac congeners was the tetrazole-promoted coupling between a sialic acid derivative and an silyl cytidine phosphoramidite. The presence or absence of electron-withdrawing substituents at C-5 and C-7 of the sialic acid was found to affect the phosphite product yields. However, quenching the promotor at low temperature with diisopropylethylamine and purifying the products by size-exclusion chromatography led to consistantly high yields (80–95%) for the coupling of each sialic acid.;Oxidation of the phosphites was accomplished with dimethyldioxirane, using a procedure developed in this laboratory, to afford the phosphates in quantitative yield. Deprotection of the silyl phosphorus protecting group was achieved by a palladium-catalyzed ester transfer reaction. The creation of the phosphate anion significantly decreased the rate of elimination in the subsequent basic hydrolysis steps. Following the removal of the hydroxyl and carboxylate protecting groups, the enzymatic substrates were provided in good yield and purity.;Five of the seven synthetic CMP-Neu5Ac derivatives were successfully transferred by the α2,3- and α2,6-sialyltransferases to lactose and lactosamine acceptors. Three naturally occurring CMP-Neu5Ac analogs modified at C-5 of sialic acid were accepted by both enzymes. Also, two unnatural congeners modified at C-5 and C-9 were accepted by the transferases. Through these reactions, a better understanding of the functional group tolerances of two sialyltransferases has been obtained.
机译：唾液酸是通常在动物糖缀合物的末端发现的九碳单糖，已知是生物识别的重要位点。将唾液酸类似物掺入寡糖的一种有效方法是利用唾液酸转移酶，该酶将唾液酸从供体化合物胞苷单膦酸-N-乙酰神经氨酸（CMP-Neu5Ac）区域和立体选择性转移到几种乳糖和乳糖胺上。派生的受体。尽管由于难以合成必需的CMP-Neu5Ac糖供体而对供体特异性了解较少，但唾液酸转移酶已显示出可耐受多种受体修饰。因此，CMP-Neu5Ac类似物的化学合成（适合引入衍生化的唾液酸）是这项工作的重点。; CMP-Neu5Ac同源物合成的关键步骤是四唑促进了一个唾液酸衍生物和甲硅烷基胞苷亚磷酰胺。发现唾液酸的C-5和C-7处是否存在吸电子取代基会影响亚磷酸酯产物的产率。然而，在低温下用二异丙基乙胺淬灭促进剂，并通过尺寸排阻色谱法纯化产物，可得到始终很高的产率（80-95％），可偶联每种唾液酸。亚磷酸酯的氧化是用二甲基二环氧乙烷完成的，该实验室开发的方法，可定量获得磷酸盐。甲硅烷基磷保护基的脱保护是通过钯催化的酯转移反应实现的。磷酸根阴离子的产生显着降低了随后的碱性水解步骤中的消除速率。除去羟基和羧酸酯保护基团后，酶底物的产率和纯度都很高。; 7种合成的CMP-Neu5Ac衍生物中有5种被α2,3-和α2,6-唾液酸转移酶成功转移到乳糖和乳糖胺受体。两种酶均接受在唾液酸的C-5处修饰的三个天然存在的CMP-Neu5Ac类似物。而且，在C-5和C-9处修饰的两个非天然同源物被转移酶接受。通过这些反应，已获得对两种唾液酸转移酶的官能团耐受性的更好理解。

著录项

  • 作者

    Chappell, Mark Donald.;

  • 作者单位

    University of Colorado at Boulder.;

  • 授予单位 University of Colorado at Boulder.;
  • 学科 Chemistry Biochemistry.;Chemistry Organic.
  • 学位 Ph.D.
  • 年度 1999
  • 页码 187 p.
  • 总页数 187
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号