5-acetamido-3,5-dideoxy-3-fluoro-D-erythro-L-manno-2-nonulopyranosonic acid

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-acetamido-3,5-dideoxy-3-fluoro-D-erythro-L-manno-2-nonulopyranosonic acid
• 英文别名: D-ery-L-manNon2ulo3F5NAc-onic；(3R,4R,5R,6R)-5-acetamido-3-fluoro-2,4-dihydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxane-2-carboxylic acid
• 化学式: C₁₁H₁₈FNO₉
• 分子量: 327.264
• InChiKey: ALJLGESFXXDPKH-AYDOOZNRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.4
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  177
• 氢给体数：
  7
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  5-acetamido-3,5-dideoxy-3-fluoro-D-erythro-L-manno-2-nonulopyranosonic acid 、 甲基 4-O-BETA-D-半乳糖基-BETA-D-吡喃葡萄糖苷 在 Pasteurella multocida sialyltransferase Tris-HCl buffer 、 CMP-唾液酸合成酶 、 magnesium chloride 作用下， 以13%的产率得到methyl O-(5-acetamido-3,5-dideoxy-3-fluoro-D-erythro-β-L-manno-2-nonulopyranosylonic acid)-(2-3)-O-β-D-galactopyranosyl-(1-4)-β-D-glucopyranoside
  参考文献：
  名称：

  Enzymatic Synthesis of Fluorinated Mechanistic Probes for Sialidases and Sialyltransferases

  摘要：

  A general, convenient, and efficient enzymatic approach for producing fluorinated mechanistic probes for sialidases and sialyltransferases is described. Other than the reported sialyltransferase inhibitor CMP-3F(axial)Neu5Ac, CIVIP-3F (equatorial)Sia derivatives (in which Sia is Neu5Ac or Neu5Gc) have been synthesized along with CMP-3F (axial)Neu5Gc and CMP-3F(axia/)KDN as novel inhibitors and important mechanistic probes for sialyltransferases. 3-Fluoro-sialosides have been enzymatically synthesized and could be used as potential inhibitors and mechanistic probes for sialidases and as probes for sialic acid-binding proteins.

  DOI：

  10.1021/ja072687u
• 作为产物：
  描述：

  N-acetyl neuraminic acid 在 吡啶 、 甲醇 、 三氟甲磺酸三甲基硅酯 、 Selectfluor 、 sodium hydroxide 作用下， 以 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 77.0h， 生成 5-acetamido-3,5-dideoxy-3-fluoro-D-erythro-L-manno-2-nonulopyranosonic acid
  参考文献：
  名称：

  Selective Inhibition of Sialic Acid-Based Molecular Mimicry in Haemophilus influenzae Abrogates Serum Resistance

  摘要：

  Pathogens such as non-typeable Haemophilus influenzae (NTHi) evade the immune system by presenting host-derived sialic acids. NTHi cannot synthesize sialic acids and therefore needs to utilize sialic acids originating from host tissue. Here we report sialic acid-based probes to visualize and inhibit the transfer of host sialic acids to NTHi. Inhibition of sialic acid utilization by NTHi enhanced serum-mediated killing. Furthermore, in an in vitro model of the human respiratory tract, we demonstrate efficient inhibition of sialic acid transfer from primary human bronchial epithelial cells to NTHi using bioorthogonal chemistry.

  DOI：

  10.1016/j.chembiol.2018.05.018

文献信息

• The synthesis of some mechanistic probes for sialic acid processing enzymes and the labeling of a sialidase from <i>Trypanosoma rangeli</i>
  作者：Andrew G Watts、Stephen G Withers

  DOI：10.1139/v04-125

  日期：2004.11.1

  Sialyl hydrolases, trans-sialidases, and sialyl transferases are biologically important enzymes that are responsible for the incorporation and removal of sialic acid residues, which decorate many cell surface glycocongugates. Two fluorinated sialic acid derivatives have been synthesized as mechanism-based inactivators, to probe the catalytic mechanisms through which sialidases and trans-sialidases operate. Both compounds are known to be covalent inactivators of a trans-sialidase from Trypanosoma cruzi. Here, 3-fluorosialosyl fluoride has been found to covalently label the catalytic nucleophile of a sialidase from T. rangeli, and the residue involved is shown to be Tyr346 within the sequence DENSGYSSVL. This is the first demonstration that sialidases operate through a covalent glycosyl-enzyme intermediate, strongly suggesting a common catalytic mechanism amongst all members of the sialidase superfamily. CMP-3-fluoro sialic acid is a competitive inhibitor of sialyl transferases and was synthesized via a two-step enzymatic process from commercially available N-acetyl mannosamine, 3-fluoropyruvic acid, and cytidine triphosphate in around 84% yield.Key words: sialidase, mechanism, labeling, nucleophile, inhibitor.

  唾液酸水解酶、转唾液酶和唾液酸转移酶是生物学上重要的酶，负责将唾液酸残基纳入或去除许多细胞表面糖蛋白中。已合成两种氟代唾液酸衍生物作为机理基础失活剂，以探究唾液酸水解酶和转唾液酶的催化机制。这两种化合物已知是Trypanosoma cruzi的一种转唾液酶的共价失活剂。在这里，发现3-氟唾液酸氟化物能共价标记T. rangeli的一种唾液酸水解酶的催化亲核物，涉及的残基为DENSGYSSVL序列中的Tyr346。这是首次证明唾液酸水解酶通过共价糖基-酶中间体进行催化，强烈暗示唾液酸水解酶超家族的所有成员之间存在共同的催化机制。CMP-3-氟唾液酸是一种唾液酸转移酶的竞争性抑制剂，通过从商业可得的N-乙酰甘露胺、3-氟丙酮酸和胞嘧啶三磷酸的两步酶法过程中合成，产率约为84%。关键词：唾液酸水解酶、机制、标记、亲核物、抑制剂。
• Enzymatic Synthesis of Fluorinated Mechanistic Probes for Sialidases and Sialyltransferases
  作者：Harshal A. Chokhawala、Hongzhi Cao、Hai Yu、Xi Chen

  DOI：10.1021/ja072687u

  日期：2007.9.1

  A general, convenient, and efficient enzymatic approach for producing fluorinated mechanistic probes for sialidases and sialyltransferases is described. Other than the reported sialyltransferase inhibitor CMP-3F(axial)Neu5Ac, CIVIP-3F (equatorial)Sia derivatives (in which Sia is Neu5Ac or Neu5Gc) have been synthesized along with CMP-3F (axial)Neu5Gc and CMP-3F(axia/)KDN as novel inhibitors and important mechanistic probes for sialyltransferases. 3-Fluoro-sialosides have been enzymatically synthesized and could be used as potential inhibitors and mechanistic probes for sialidases and as probes for sialic acid-binding proteins.
• Selective Inhibition of Sialic Acid-Based Molecular Mimicry in Haemophilus influenzae Abrogates Serum Resistance
  作者：Torben Heise、Jeroen D. Langereis、Emiel Rossing、Marien I. de Jonge、Gosse J. Adema、Christian Büll、Thomas J. Boltje

  DOI：10.1016/j.chembiol.2018.05.018

  日期：2018.10

  Pathogens such as non-typeable Haemophilus influenzae (NTHi) evade the immune system by presenting host-derived sialic acids. NTHi cannot synthesize sialic acids and therefore needs to utilize sialic acids originating from host tissue. Here we report sialic acid-based probes to visualize and inhibit the transfer of host sialic acids to NTHi. Inhibition of sialic acid utilization by NTHi enhanced serum-mediated killing. Furthermore, in an in vitro model of the human respiratory tract, we demonstrate efficient inhibition of sialic acid transfer from primary human bronchial epithelial cells to NTHi using bioorthogonal chemistry.