CMP-sialic acid

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 英文名称: CMP-sialic acid
• 英文别名: Cytidine-5'-monophospho-N-acetylneuraminic acid sodium salt；sodium;(2S,4S,5R,6R)-5-acetamido-2-[[(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxane-2-carboxylate
• 化学式: C₂₀H₃₀N₄O₁₆P*Na
• 分子量: 636.439
• InChiKey: VFRHSOGUONIUOR-ZJZPELACSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -9.6
• 重原子数：
  42
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  324
• 氢给体数：
  9
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  3-{[3-乙酰氨基-5-羟基-6-(羟基甲基)-4-{[3,4,5-三羟基-6-(羟基甲基)四氢-2H-吡喃-2-基]氧基}四氢-2H-吡喃-2-基]氧基}-2-氨基丁酸 、 CMP-sialic acid 反应 72.0h， 以24%的产率得到O-(5-acetamido-3,5-dideoxy-α-D-glycero-D-galacto-nonulopyranosylonic acid)-(2-3)-O-(β-galactopyranosyl)-(1-3)-(2-acetamido-2-deoxy-α-D-galactopyranosyl)-(1-3)-L-threonine
  参考文献：
  名称：

  Multienzyme System for Synthesis of the Sialylated Thomsen–Friedenreich Antigen Determinant

  摘要：

  DOI：

  10.1002/(sici)1099-0690(199901)1999:1<107::aid-ejoc107>3.0.co;2-m
• 作为产物：
  描述：

  N-乙酰神经氨酸水合物 、 胞苷-5’-三磷酸 反应 36.0h， 以67%的产率得到CMP-sialic acid
  参考文献：
  名称：

  Multienzyme System for Synthesis of the Sialylated Thomsen–Friedenreich Antigen Determinant

  摘要：

  DOI：

  10.1002/(sici)1099-0690(199901)1999:1<107::aid-ejoc107>3.0.co;2-m

文献信息

• Chemo-enzymatic synthesis of sialylated oligosaccharides
  申请人：DeFrees Shawn

  公开号：US20050032742A1

  公开（公告）日：2005-02-10

  In vitro/cell-free process of preparing a sialylated oligosaccharides are described. The sialylated oligosaccharides include gangliosides. The oligosaccharides linked to various moieties including sphingoids and ceramides. Novel compounds that comprise sphingoid groups are disclosed. The compounds include sialylated oligosaccharides including gangliosides as well as various sphingoids and ceramides.

  描述了一种制备唾液酸寡糖的体外/无细胞过程。这些唾液酸寡糖包括神经节苷脂。这些寡糖与各种基团如鞘氨醇和鞘氨醇脂结合。还披露了包含鞘氨醇基团的新化合物。这些化合物包括唾液酸寡糖，其中包括神经节苷脂以及各种鞘氨醇和鞘氨醇脂。
• Chemoenzymatic synthesis of a trimeric ganglioside GM3 analogue
  作者：Marion A. Earle、Sukhdev Manku、Philip G. Hultin、Hong Li、Monica M. Palcic

  DOI：10.1016/s0008-6215(97)00085-2

  日期：1997.6

  N-acetyllactosamine acceptors, and its Vmax was 1% of that measured for the LacNAc acceptor. Preparative-scale sialylation using this enzyme afforded a trimeric cluster of the ganglioside GM3 oligosaccharide in good yield. The NMR spectra of the trimeric GM3 analogue suggest that the oligosaccharide conformation is not significantly perturbed by this level of clustering.

  使用三氯乙亚氨酸酯法制备基于2-硝基-2-（羟甲基）丙烷-1,3-二醇的三聚体β-乳糖基簇。动力学研究表明，该簇是大鼠肝脏α-（2-> 3）-唾液酸转移酶的有效受体。它的KM可与单体乳糖和N-乙酰基乳糖胺受体的KM相媲美，并且其Vmax为LacNAc受体测得的Vmax的1％。使用该酶的制备规模的唾液酸化以良好的产率提供了神经节苷脂GM3寡糖的三聚体簇。三聚体GM3类似物的NMR光谱表明，这种聚类水平不会明显干扰寡糖构象。
• Recognition of Complex Core-Fucosylated N-Glycans by a Mini Lectin
  作者：Aurore Cabanettes、Lukas Perkams、Carolina Spies、Carlo Unverzagt、Annabelle Varrot

  DOI：10.1002/anie.201805165

  日期：2018.8.6

  The mini fungal lectin PhoSL was recombinantly produced and characterized. Despite a length of only 40 amino acids, PhoSL exclusively recognizes N‐glycans with α1,6‐linked fucose. Core fucosylation influences the intrinsic properties and bioactivities of mammalian N‐glycoproteins and its level is linked to various cancers. Thus, PhoSL serves as a promising tool for glycoprofiling. Without structural

  微型真菌凝集素PhoSL重组生产和表征。尽管只有40个氨基酸，PhoSL只能识别具有α1,6-连接岩藻糖的N-聚糖。核心岩藻糖基化影响哺乳动物N-糖蛋白的固有特性和生物活性，其水平与各种癌症有关。因此，PhoSL可以用作糖谱分析的有前途的工具。没有结构优先权，就使用锌异常信号解析了晶体结构，并揭示了交错的三聚体，形成了一种称为β-PrismIII的新型蛋白质折叠。用PhoSL将3个8到12个糖的双触角岩藻糖基化N-聚糖叠氮化物共结晶。由此产生的高度解析的结构详细说明了如何通过这种小蛋白质对α1,6-岩藻糖基化的N-聚糖进行独家识别。
• An Essential Epitope of Anti-MUC1 Monoclonal Antibody KL-6 Revealed by Focused Glycopeptide Library
  作者：Naoki Ohyabu、Hiroshi Hinou、Takahiko Matsushita、Ryukou Izumi、Hiroki Shimizu、Keiko Kawamoto、Yoshito Numata、Hiroko Togame、Hiroshi Takemoto、Hirosato Kondo、Shin-Ichiro Nishimura

  DOI：10.1021/ja903361f

  日期：2009.12.2

  Human serum Krebs von den Lungen-6 (KL-6) antigen, a high-molecular-weight glycoprotein classified as a polymorphic epithelial mucin (MUC1), is a biomarker of diseases such as interstitial pneumonia, lung adenocarcinoma, breast cancer, colorectal adenocarcinoma, and hepatocellular carcinoma. Anti-KL-6 monoclonal antibody (anti-KL-6 MAb) is therefore a potential diagnostic and therapeutic reagent. Although glycosylation at Thr/Ser residues of the tandem-repeating MUC1 peptides appears to determine the disease-associated antigenic structures of KL-6, an essential epitope structure recognized by anti-KL-6 MAb remains unclear. In the present study, a novel compound library of synthetic MUC1 glycopeptides allowed the first rapid and precise evaluation of the specific epitope structure of anti-KL-6 MAb by combined use of a tailored glycopeptides library and common ELISA protocol. We demonstrated that the minimal antigenic structure, an essential epitope, recognized by anti-KL-6 MAb is a heptapeptide sequence Pro-Asp-Thr-Arg-Pro-Ala-Pro (PDTRPAP), in which the Thr residue is modified by Neu5Ac alpha 2,3Gal beta 1,3GalNAc alpha (2,3-sialyl T antigen, core 1-type O-glycan). Anti-KL-6 MAb did not bind with other tumor-relevant antigens, such as GalNA alpha(Tn), Neu5Ac alpha 2,6GalNAc alpha(STn), and Gal beta 1,3GalNAc alpha (T), except for Neu5Ac alpha 2,3Gal beta 1,3(Neu5Ac alpha 2,6) GalNAc alpha(2,3/2,6-disialyl T). However, anti-KL-6 MAb could not differentiate the above minimal antigenic glycopepticle from some core 2-based glycopeptides involving this crucial epitope structure and showed a similar binding affinity toward these compounds, indicating that branching at the O-6 position of GalNAc residue does not influence the interaction of anti-KL-6 MAb with some MUC1 glycoproteins involving an essential epitope. Actually, anti-KL-6 MAb reacts with 2,3/2,6-disialyl T having a 2,3-sialyl T component. This is why anti-KL-6 MAb often reacts with various kinds of tumor-derived MUC1 glycoproteins as well as a clinically important MUC1 glycoprotein biomarker of interstitial pneumonia, namely KL-6, originally discovered as a circulating pulmonary adenocarcinoma-associated antigen. In other words, combined use of anti-KL-6 MAb and some probes that can differentiate the sugars substituted at the O-6 position of the GalNAc residue in MUC1 glycopeptides including the PDTRPAP sequence might be a promising diagnostic protocol for individual disease-specific biomarkers. It was also revealed that glycosylation at neighboring Thr/Ser residues outside the immunodominant PDTRPAP motif strongly influences the interaction between anti-KL-6 MAb and MUC1 glycopeptides involving the identified epitope. Our novel strategy will greatly facilitate the processes for the identification of the tumor-specific and strong epitopes of various known anti-MUC1 MAbs and allow for their practical application in the generation of improved antibody immunotherapeutics, diagnostics, and MUC1-based cancer vaccines.
• Ligand Recognition by E-Selectin: Synthesis, Inhibitory Activity and Conformational Analysis of Bivalent Sialyl Lewis x Analogs
  作者：Shawn A. DeFrees、Winfried Kosch、William Way、James C. Paulson、Subramanian Sabesan、Randall L. Halcomb、Dee-Hua Huang、Yoshitaka Ichikawa、Chi-Huey Wong

  DOI：10.1021/ja00106a008

  日期：1995.1

  Several sialyl Lewis x dimers anchored onto a galactose template or attached to 1,4-butanediol or 1,5-pentanediol have been prepared chemoenzymatically and evaluated as inhibitors of E-selectin-mediated cell adhesion. Two monosaccharide units were simultaneously incorporated (i.e., Gal, NeuAc, Fuc) by a glycosyltransferase into a chemically synthesized core structure containing GlcNAc and Gal. Each of the galactose-anchored dimers had higher activity than the sialyl Lewis x pentasaccharide la, with the general trend being 3,6-linked > 2,3 greater than or equal to 4,6 greater than or equal to 2,6 monomer. The dimers linked to butanediol or pentanediol showed the same level of activity as the pentasaccharide monomer. Conformational analysis of these dimers with NMR indicated that each sialyl Lewis x domain of the dimers retains the same conformation as the monomer. The differences in activity of the dimers most likely derive from differences in the relative orientation and distance between the monomer domains, suggesting the importance of the linker used in the preparation of dimers.