4-脱氧-4-氟-D-半乳糖 | 238418-56-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 4-脱氧-4-氟-D-半乳糖
• 英文名称: 4-deoxy-4-fluoro-D-galactose
• 英文别名: 4-deoxy-4-fluorogalactose；Gal4F；4-fluoro-D-4-deoxy-galactose；4-fluoro-ξ-D-4-deoxy-galactopyranose；4-fluorogalactose；4-Fluoro-4-deoxy-D-galactopyranose；(3R,4R,5R,6R)-5-fluoro-6-(hydroxymethyl)oxane-2,3,4-triol
• CAS: 238418-56-9
• 化学式: C₆H₁₁FO₅
• mdl: MFCD00057524
• 分子量: 182.149
• InChiKey: FIHYONSINSKFAH-SVZMEOIVSA-N

物化性质

• 沸点：
  370.1±42.0 °C(Predicted)
• 密度：
  1.59±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.1
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  90.2
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-脱氧-4-氟-D-半乳糖 在 lithium hydroxide 、 磷酸 、 sodium acetate 作用下， 反应 5.33h， 生成 4-Deoxy-4-fluoro-β-D-glucopyranosyl
  参考文献：
  名称：

  Synthesis of UDP-4-deoxy-4-fluoroglucose and UDP-4-deoxy-4-fluorogalactose and their Interactions with Enzymes of Nucleotide Sugar Metabolism

  摘要：

  Fluorinated carbohydrates can be used as probes of enzymatic active sites. We report the synthesis of 4-deoxy-4-fluoro-alpha-D-galactose-1-phosphate and the substrate analogues of UDP-galactose, UDP-4-deoxy-4-fluoro-alpha-D-galactose (UDP-FGal), and of UDP-glucose, UDP-4-deoxy-4-fluoro-alpha-D-glucose (UDP-FGlc), which may be useful in analyzing the binding properties of enzymes that utilize nucleotide sugars as substrates. As a first step in this study, we determine the kinetic and inhibition parameters for UDP-FGal and UDP-FGlc interacting with UDP-glucose dehydrogenase and UDP-galactose 4-epimerase. UDP-FGlc is a substrate for bovine liver UDP-glucose dehydrogenase: K-m = 30.2 +/- 4.5 mu M slightly higher than the value 9.6 +/- 0.7 mu M for UDP-glucose, and V-mUDP-FGlc = 046V (mUDP-Glc). UDP-FGal is not a substrate for UDP-glucose dehydrogenase but is a competitive inhibitor with respect to UDP-glucose (K-i = 19.9 +/- 6.6 mu M). These analogs also bind to UDP-galactose 4-epimerase from E. coli with dissociation constants K-d of 1.4 and 1.1 mM for UDP-FGlc and UDP-FGal, respectively.

  DOI：

  10.1021/jo00102a024
• 作为产物：
  描述：

  1-硫代-b-甲基葡萄糖甙-4-甲基苯酯 在 吡啶 、 4-二甲氨基吡啶 、 N-碘代丁二酰亚胺 、 三氟甲磺酸酐 、 silica gel supported sodium hydrogen sulfate 、 β-galactosidase from bovine testes 、 sodium methylate 、 silver trifluoromethanesulfonate 、 对甲苯磺酸 、 溶剂黄146 、 bovine serum albumin 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 134.0h， 生成 4-脱氧-4-氟-D-半乳糖
  参考文献：
  名称：

  Synthesis and biological evaluation of a novel MUC1 glycopeptide conjugate vaccine candidate comprising a 4’-deoxy-4’-fluoro-Thomsen–Friedenreich epitope

  摘要：

  选择性抗癌疫苗的开发，提供增强对肿瘤复发和转移的保护，一直是科学界研究的焦点。与肿瘤相关的糖蛋白MUC1代表了癌症免疫疗法的一个成熟靶点，并已被用于构建各种合成疫苗候选物。然而，许多这些疫苗原型存在固有的低免疫原性，并容易在体内迅速降解。为了克服这些缺点，已制备了新型氟化MUC1糖肽-BSA/TTox结合疫苗。用4’F-TF-MUC1-TTox结合物免疫小鼠导致强烈的免疫反应，覆盖了对MUC1的自然耐受性，并产生了选择性的IgG抗体，与MCF-7人类癌细胞上的原生MUC1表位发生交叉反应。

  DOI：

  10.3762/bjoc.11.15

文献信息

• Characterisation of a Bacterial Galactokinase with High Activity and Broad Substrate Tolerance for Chemoenzymatic Synthesis of 6-Aminogalactose-1-Phosphate and Analogues
  作者：Kun Huang、Fabio Parmeggiani、Edward Pallister、Chuen-Jiuan Huang、Fang-Fang Liu、Qian Li、William R. Birmingham、Peter Both、Baptiste Thomas、Li Liu、Josef Voglmeir、Sabine L. Flitsch

  DOI：10.1002/cbic.201700477

  日期：2018.2.16

  Furnishing phosphates: A galactokinase from L. grimontii (LgGalK) has been identified and characterised; it shows broad substrate specificity towards different nucleotide phosphates and monosaccharides. This enzyme, in combination with a galactose oxidase variant was used in the chemoenzymatic synthesis of a panel of 6‐aminogalactose‐1‐phosphate analogues.

  提供磷酸盐：已经鉴定并鉴定了来自格氏乳杆菌的半乳糖激酶（LgGalK）；它对不同的核苷酸磷酸和单糖显示出广泛的底物特异性。该酶与半乳糖氧化酶变体结合在一起，用于化学酶合成6-氨基半乳糖-1-磷酸类似物。
• SUGAR CHAIN CONTAINING 4-POSITION HALOGENATED GALACTOSE AND APPLICATION THEREOF
  申请人：Nishimura Shin-Ichiro

  公开号：US20090018327A1

  公开（公告）日：2009-01-15

  The present invention is directed to, for example, an oligosaccharide having at an end thereof a 4-position halogenated galactose residue represented by formula (I): (wherein X represents a halogen atom, and R represents a monosaccharide, an oligosaccharide, or a carrier), a transferase inhibitor containing the oligosaccharide, and a method for inhibiting sugar chain elongation reaction in the presence of glycosyltransferase, the method including employing the inhibitor. The invention also provides a method for producing a 4-position halogenated galactose sugar nucleotide represented by formula (II): (wherein each of R 1 to R 3 represents a hydroxyl group, an acetyl group, a halogen atom, or a hydrogen atom; X represents a halogen atom; and M represents a hydrogen ion or a metal ion), wherein the method employs bacterium-derived galactokinase and bacterium-derived hexose-1-phosphate uridylyltransferase. The invention is also directed to a sugar chain containing 4-position halogenated galactose envisaged to be employed as drugs and other materials, and to applications of the compound.

  本发明涉及一种寡糖，其末端具有由公式(I)表示的4位卤代半乳糖残基：（其中X代表卤素原子，R代表单糖，寡糖或载体），含有该寡糖的转移酶抑制剂，以及在存在糖基转移酶时抑制糖链延长反应的方法，该方法包括使用该抑制剂。该发明还提供了一种生产由公式(II)表示的4位卤代半乳糖核苷酸的方法：（其中R1至R3中的每一个代表羟基、乙酰基、卤素原子或氢原子；X代表卤素原子；M代表氢离子或金属离子），该方法利用细菌来源的半乳糖激酶和细菌来源的己糖-1-磷酸尿苷转移酶。本发明还涉及一种含有4位卤代半乳糖的糖链，可用作药物和其他材料，并涉及该化合物的应用。
• Rapid Screening of Diverse Biotransformations for Enzyme Evolution
  作者：Emily E. Kempa、James L. Galman、Fabio Parmeggiani、James R. Marshall、Julien Malassis、Clement Q. Fontenelle、Jean-Baptiste Vendeville、Bruno Linclau、Simon J. Charnock、Sabine L. Flitsch、Nicholas J. Turner、Perdita E. Barran

  DOI：10.1021/jacsau.1c00027

  日期：2021.4.26

  of enzymes, in different formats, achieving sample throughputs equivalent to ∼40 s per sample. The heat map output allows rapid selection of active enzymes within 96-well plates facilitating identification of industrially relevant biocatalysts. This DiBT-MS screening workflow has been applied to the directed evolution of a phenylalanine ammonia lyase (PAL) as a case study, enhancing its activity toward

  缺乏无标签的高通量筛选技术的缺乏成为鉴定活性和选择性生物催化剂的主要瓶颈，变异体的数量通常超过了传统分析平台在实际时间范围内评估其活性的能力。在这里，我们展示了将生物转化直接输注到质谱仪（DiBT-MS）筛查中应用到各种格式的多种酶的过程，每个样品的样品通量约为40 s。热图输出允许在96孔板内快速选择活性酶，从而有助于鉴定工业上相关的生物催化剂。作为案例研究，该DiBT-MS筛选工作流程已应用于苯丙氨酸氨裂合酶（PAL）的定向进化，增强了其对富含电子的肉桂酸衍生物的活性，这些衍生物与木质纤维素生物质的降解有关。筛选平台的其他好处包括发现具有新颖活性的生物催化剂（激酶，亚胺还原酶），并引入了离子迁移技术，可以更加可靠地鉴定产品。
• Synthesis and biological evaluation of a novel MUC1 glycopeptide conjugate vaccine candidate comprising a 4’-deoxy-4’-fluoro-Thomsen–Friedenreich epitope
  作者：Manuel Johannes、Maximilian Reindl、Bastian Gerlitzki、Edgar Schmitt、Anja Hoffmann-Röder

  DOI：10.3762/bjoc.11.15

  日期：——

  The development of selective anticancer vaccines that provide enhanced protection against tumor recurrence and metastasis has been the subject of intense research in the scientific community. The tumor-associated glycoprotein MUC1 represents a well-established target for cancer immunotherapy and has been used for the construction of various synthetic vaccine candidates. However, many of these vaccine prototypes suffer from an inherent low immunogenicity and are susceptible to rapid in vivo degradation. To overcome these drawbacks, novel fluorinated MUC1 glycopeptide-BSA/TTox conjugate vaccines have been prepared. Immunization of mice with the 4’F-TF-MUC1-TTox conjugate resulted in strong immune responses overriding the natural tolerance against MUC1 and producing selective IgG antibodies that are cross-reactive with native MUC1 epitopes on MCF-7 human cancer cells.

  选择性抗癌疫苗的开发，提供增强对肿瘤复发和转移的保护，一直是科学界研究的焦点。与肿瘤相关的糖蛋白MUC1代表了癌症免疫疗法的一个成熟靶点，并已被用于构建各种合成疫苗候选物。然而，许多这些疫苗原型存在固有的低免疫原性，并容易在体内迅速降解。为了克服这些缺点，已制备了新型氟化MUC1糖肽-BSA/TTox结合疫苗。用4’F-TF-MUC1-TTox结合物免疫小鼠导致强烈的免疫反应，覆盖了对MUC1的自然耐受性，并产生了选择性的IgG抗体，与MCF-7人类癌细胞上的原生MUC1表位发生交叉反应。
• Synthesis of UDP-4-deoxy-4-fluoroglucose and UDP-4-deoxy-4-fluorogalactose and their Interactions with Enzymes of Nucleotide Sugar Metabolism
  作者：Marie-Christine Chapeau、Perry A. Frey

  DOI：10.1021/jo00102a024

  日期：1994.11

  Fluorinated carbohydrates can be used as probes of enzymatic active sites. We report the synthesis of 4-deoxy-4-fluoro-alpha-D-galactose-1-phosphate and the substrate analogues of UDP-galactose, UDP-4-deoxy-4-fluoro-alpha-D-galactose (UDP-FGal), and of UDP-glucose, UDP-4-deoxy-4-fluoro-alpha-D-glucose (UDP-FGlc), which may be useful in analyzing the binding properties of enzymes that utilize nucleotide sugars as substrates. As a first step in this study, we determine the kinetic and inhibition parameters for UDP-FGal and UDP-FGlc interacting with UDP-glucose dehydrogenase and UDP-galactose 4-epimerase. UDP-FGlc is a substrate for bovine liver UDP-glucose dehydrogenase: K-m = 30.2 +/- 4.5 mu M slightly higher than the value 9.6 +/- 0.7 mu M for UDP-glucose, and V-mUDP-FGlc = 046V (mUDP-Glc). UDP-FGal is not a substrate for UDP-glucose dehydrogenase but is a competitive inhibitor with respect to UDP-glucose (K-i = 19.9 +/- 6.6 mu M). These analogs also bind to UDP-galactose 4-epimerase from E. coli with dissociation constants K-d of 1.4 and 1.1 mM for UDP-FGlc and UDP-FGal, respectively.