2,3,4,6-tetraacetyl-<2-(2-azidoethoxy)ethyl>-β-D-galactoside | 153252-36-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2,3,4,6-tetraacetyl-<2-(2-azidoethoxy)ethyl>-β-D-galactoside
• 英文别名: 1-azido-3-oxapent-5-yl 2,3,4,6-tetra-O-acetyl-β-D-galactopyranoside；2-(2-azidoethoxy)ethyl 2,3,4,6-tetra-O-acetyl-β-D-galactopyranoside；5-azido-3-oxapentyl 2,3,4,6-tetra-O-acetyl-α-D-galactopyranoside；5-azido-3-oxapentyl 2,3,4,6-tetra-O-acetyl-β-D-galactopyranoside；5-azido-3-oxapentyl-2,3,4,6-tetra-O-acetyl-β-galactopyranoside；beta-D-tetraacetylgalactopyranoside-PEG1-N3；[(2R,3S,4S,5R,6R)-3,4,5-triacetyloxy-6-[2-(2-azidoethoxy)ethoxy]oxan-2-yl]methyl acetate
• CAS: 153252-36-9
• 化学式: C₁₈H₂₇N₃O₁₁
• 分子量: 461.426
• InChiKey: OFRJNIAQTXDUKV-DISONHOPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  32
• 可旋转键数：
  16
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  147
• 氢给体数：
  0
• 氢受体数：
  13

制备方法与用途

生物活性

β-D-tetraacetylgalactopyranoside-PEG1-N3 是一种可降解 (cleavable) 的含 1 个单元 PEG 的 ADC linker，可用于合成抗体偶联药物 (ADC)。

靶点

Cleavable

反应信息

• 作为反应物：
  描述：

  2,3,4,6-tetraacetyl-<2-(2-azidoethoxy)ethyl>-β-D-galactoside 在 palladium on activated charcoal 氢气 、 sodium methylate 、 溶剂黄146 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、344.74 kPa 条件下， 反应 44.0h， 生成 17-demethoxy-17-{[2-(2-β-galactopyranosylethyl)ethyl]amino}geldanamycin
  参考文献：
  名称：

  Synthesis and Enzyme-Specific Activation of Carbohydrate−Geldanamycin Conjugates with Potent Anticancer Activity

  摘要：

  Geldanamycin (GA) is a potent anticancer antibiotic that inhibits Hsp90. Its potential clinical utility is hampered by its severe toxicity. To alleviate this problem, we synthesized a series of carbohydrate - geldanamycin conjugates for enzyine-specific activation to increase tumor selectivity. The conjugation was carried out at the C-17-position of GA. Their anticancer activity was tested in a number of cancer cell lines. The enzyme-specific activation of these conjugates M ion was evaluated with beta-galactosidase and beta-glucosidase. Evidently. glycosylation of C-17-pasition converted GA to an inactive prodrug before enzyme cleavage. Glucose-GA, as positive control, showed anticancer activity with IC50 of 70.2- 380.9 nM in various cancer cells by beta-glucocsidase activation inside of the tumor cells, which was confirmed by 3-fold inhibition using beta-glucasidase. specific inhibitor [2,5-dihydroxyniethy-3,4-dihydroxypyrrolidine (DMDP)]. Compared to glucose- GA, galactose- and lactose-GA conjugates exhibited much less activity with IC50 greater than 8000-25 000 nM. However, when galactose- and lactose-GA, were incubated with beta-galactosidase in the cells, their anticancer activity was enhanced by 3- to 40-fold. The results suggest, that GA can be inactivated by glycosylation of C-17-position and reactivated for anticancer activity by beta-galactosidase. Therefore, galactose-GA can be exploited in antibody-directed enzyme prodrug therapy (ADEPT) with beta-galactosidase for enzyme-specific activation in tumors. to increase tumor selectivity.

  DOI：

  10.1021/jm049693a
• 作为产物：
  描述：

  beta-D-半乳糖五乙酸酯 在 sodium azide 、 silver trifluoroacetate 、 四氯化锡 、 四丁基碘化铵 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.17h， 生成 2,3,4,6-tetraacetyl-<2-(2-azidoethoxy)ethyl>-β-D-galactoside
  参考文献：
  名称：

  多价凝集素与碳水化合物相互作用的最佳糖簇的合理设计与合成：连接臂的影响

  摘要：

  多价糖簇的设计需要将通过连接臂功能化的生物学相关的碳水化合物表位缀合到多价核心支架上。结合酰胺部分和/或苯环的三种结构修饰的三乙二醇类似物的数克级合成，可方便地获得一系列具有不同水溶性和刚性的碳水化合物探针。通过构象分析进行灵活性的评估和优选构象的确定。叠氮基官能化碳水化合物与四炔丙基化核心支架的偶联，通过Cu I高产量提供了一个包含18个四价糖簇的文库催化的叠氮化物-炔烃环加成反应（CuAAC）。评估了这些化合物与PA‐IL（来自机会性病原体铜绿假单胞菌的LecA凝集素）结合的能力。通过抑制血凝测定（HIA），酶联凝集素测定（ELLA），表面等离振子共振（SPR）和等温滴定微量量热法（ITC）进行生化评估，发现其中一种单价探针的亲和力得到了改善和前所未有的提高（K d = 5.8 μ中号），并且还为一个数字，提供这种四聚体凝集素几个新的配位体纳摩尔四价化合物。

  DOI：

  10.1002/chem.201200010

文献信息

• Synthesis and antibacterial activities of novel tyrocidine A glycosylated derivatives towards multidrug-resistant pathogens
  作者：Yan Zou、Qingjie Zhao、Chunmei Zhang、Liang Wang、Wenjuan Li、Xiang Li、Qiuye Wu、Honggang Hu

  DOI：10.1002/psc.2774

  日期：2015.7

  and functions of peptides and plays a critical role in interacting with or binding to the target molecules. Herein, based on the previously reported method for macrocyclic glycopeptide synthesis, two series of tyrocidine A glycosylated derivatives (1a–f and 2a–f) were synthesized and evaluated for their antibacterial activities to further study the structure and activity relationships (SAR). Biological

  糖基化可以对肽的性质和功能产生多方面的影响，并且在与靶分子相互作用或结合中起关键作用。在此，根据先前报道的大环糖肽合成方法，合成了两个系列的酪氨酸A糖基化衍生物（1a-f和2a-f），并对其抗菌活性进行了评估，以进一步研究其结构和活性关系（SAR）。生物学研究表明，合成的糖基化衍生物对耐甲氧西林的金黄色葡萄球菌和耐万古霉素的肠球菌具有良好的抗菌活性。。SAR研究基于各种聚糖和键联来增强生化特性，从而鉴定出几种有效的抗生素，例如1f，其治疗指数比酪氨酸A大为改善。版权所有©2015欧洲肽协会和John Wiley＆Sons ，Ltd.
• Syntheses of Novel Galoctosyl Ligands for Liposomes and the Influence of the Spacer on Accumulation in the Rat Liver.
  作者：Atsushi SASAKI、Naokazu MURAHASHI、Harutami YAMADA、Anri MORIKAWA

  DOI：10.1248/bpb.18.740

  日期：——

  We modified the surface of liposomes with galactosyl ligands. At first we determined whether or not the galactosyl moiety was exposed on the liposomes. We then investigated the effect of the ligands on the hepatic accumulation of liposomes in rats. We introduced an oligoethylene glycol moiety as a spacer. Among the various ligands tested, those with a tri-or tetraethylene glycol moiety as a spacer caused the greatest accumulation of liposomes in the liver. Liposomes bearing ligands with a tri-or tetraethylene glycol moiety as a spacer, were aggregated by Ricinus communis agglutinin. On the other hand, those modified with ligands with a mono- or diethylene glycol spacer did not clearly agglutinate. These results show the importance of a spacer between the homing device and the ligand anchor.

  我们将半乳糖基配体修饰到脂质体表面。首先，我们确定半乳糖基团是否暴露在脂质体表面。然后，我们研究了这些配体对大鼠肝脏中脂质体积累的影响。我们引入了一个聚乙二醇基团作为间隔基。在测试的各种配体中，具有三或四聚乙二醇间隔基的配体导致脂质体在肝脏中积累最多。带有三或四聚乙二醇间隔基配体的脂质体被蓖麻凝集素聚集。另一方面，修饰有单或二聚乙二醇间隔基配体的脂质体没有明显聚集。这些结果显示了归巢装置与配体锚定基之间间隔基的重要性。
• GLYCOMIMETIC COMPOUNDS AS ANTI-INFECTIOUS AGAINST PATHOGENS LECTINS
  申请人：Imberty Anne

  公开号：US20130252910A1

  公开（公告）日：2013-09-26

  The present invention relates to a calixarene-based glycosylated compound (I) having the formula: (I) wherein D is independently selected in the group comprising a —CH 2 -group, an oxygen atom, a sulphur atom, a sulfinyl group or a sulfonyl group, E is independently selected in the group comprising a hydrogen, an alkyl having from 1 to 10 carbon atoms, an aryl having from 6 to 20 carbon atoms, a nitrogen dioxide group, an azide group, an amino group, a guanidinium group, a halogen atom, a —CH 2 R group wherein R is a hydroxyl, a halogen, an amino group, a N(alkyl) 2 group, a NH(alkyl) group, or E represents a —CO—R′ wherein R′ is a hydrogen atom, a hydroxyl group or an amino, B represents a A-C group wherein A is independently selected in the group comprising an oxygen atom, a sulfur atom, a NH group or a (CH 2 ) i group, i being an integer from 1 to 10, C is independently selected in the group comprising a hydrogen, an alkyl, an alkenyl, an alkynyl, or C is a group of formula (II). The present invention also relates to a pharmaceutical composition characterized in that it comprises the said calixarene-based glycosylated compound (I), in combination with pharmaceutically acceptable carriers or diluents. The present invention also relates to the use of the said calixarene-based glycosylated compound (I) or the said pharmaceutical composition, for the manufacture of a drug intended to prevent or treat bacterial infections from pathogens that use lectins in the first steps of infection.

  本发明涉及一种基于杯芳烃的糖基化化合物（I），其化学式如下：（I）其中D在以下组中独立选择：—CH2基团、氧原子、硫原子、亚砜基或磺酰基；E在以下组中独立选择：氢、具有1至10个碳原子的烷基、具有6至20个碳原子的芳基、亚硝基团、叠氮基团、氨基、胍胺基、卤原子、— R基团（其中R是羟基、卤原子、氨基、N（烷基）2基团、NH（烷基）基团）或E代表—CO—R'（其中R'是氢原子、羟基或氨基），B代表A-C基团（其中A在以下组中独立选择：氧原子、硫原子、NH基团或（ ）i基团，i为1至10的整数），C在以下组中独立选择：氢、烷基、烯基、炔基，或C是化学式（II）的基团。本发明还涉及一种药物组合物，其特征在于它包括所述的基于杯芳烃的糖基化化合物（I），与药学上可接受的载体或稀释剂结合。本发明还涉及所述的基于杯芳烃的糖基化化合物（I）或所述的药物组合物的用途，用于制造用于预防或治疗利用凝集素进行感染起始阶段的病原体引起的细菌感染的药物。
• [EN] GLYCOMIMETIC COMPOUNDS AS ANTI-INFECTIOUS AGAINST PATHOGENS LECTINS<br/>[FR] COMPOSÉS GLYCOMIMÉTIQUES EN TANT QU'AGENTS ANTI-INFECTIEUX CONTRE DES LECTINES PATHOGÈNES
  申请人：CENTRE NAT RECH SCIENT

  公开号：WO2012076934A1

  公开（公告）日：2012-06-14

  The present invention relates to a calixarene-based glycosylated compound (I) having the formula : (I) wherein D is independently selected in the group comprising a –CH2 –group, an oxygen atom, a sulphur atom, a sulfinyl group or a sulfonyl group, E is independently selected in the group comprising a hydrogen, an alkyl having from 1 to 10 carbon atoms, an aryl having from 6 to 20 carbon atoms, a nitrogen dioxide group, an azide group, an amino group, a guanidinium group,a halogen atom, a –CH2 R group wherein R is a hydroxyl, a halogen, an amino group, a N(alkyl)2 group, a NH(alkyl) group, or E represents a –CO-R' wherein R' is a hydrogen atom, a hydroxyl group or an amino, B represents a A–C group wherein A is independently selected in the group comprising an oxygen atom, a sulfur atom, a NH group or a (CH2 )i group, i being an integer from 1 to 10, C is independently selected in the group comprising a hydrogen, an alkyl, an alkenyl, an alkynyl, or C is a group of formula (II). The present invention also relates to a pharmaceutical composition characterized in that it comprises the said calixarene-based glycosylated compound (I), in combination with pharmaceutically acceptable carriers or diluents. The present invention also relates to the use of the said calixarene-based glycosylated compound (I) or the said pharmaceutical composition, for the manufacture of a drug intended to prevent or treat bacterial infections from pathogens that use lectins in the first steps of infection.

  本发明涉及一种基于杯芳烃的糖基化化合物（I），其化学式为：（I），其中D在以下基团中独立选择：-CH2-基团、氧原子、硫原子、亚砜基团或磺基团，E在以下基团中独立选择：氢、碳原子数为1至10的烷基、碳原子数为6至20的芳基、二氧化氮基团、叠氮基团、氨基团、胍基团、卤素原子、- R基团，其中R为羟基、卤素、氨基、N（烷基）2基团、NH（烷基）基团，或E表示-CO-R'，其中R'为氢原子、羟基或氨基，B表示A-C基团，其中A在以下基团中独立选择：氧原子、硫原子、NH基团或( )i基团，i为1至10的整数，C在以下基团中独立选择：氢、烷基、烯基、炔基，或C为下式的基团（II）。本发明还涉及一种药物组合物，其特征在于它包括所述基于杯芳烃的糖基化化合物（I），结合具有药用接受的载体或稀释剂。本发明还涉及所述基于杯芳烃的糖基化化合物（I）或所述药物组合物的用途，用于制造预防或治疗利用凝集素在感染的最初阶段的病原体引起的细菌感染的药物。
• Targeting Bacterial Biofilm: A New LecA Multivalent Ligand with Inhibitory Activity
  作者：Alessandro Palmioli、Paola Sperandeo、Alessandra Polissi、Cristina Airoldi

  DOI：10.1002/cbic.201900383

  日期：2019.12.2

  antibiotic therapies. Infections caused by Pseudomonas aeruginosa are of great concern, especially for immunocompromised and cystic fibrosis patients. P. aeruginosa lectins LecA and LecB are virulence factors and play a key role in establishing biofilm; therefore, inhibition of the function of these proteins has potential in dismantling the bacterium from the protective biofilm environment and in restoring

  细菌性病原体形成生物膜是慢性感染的标志，并与增加的抗生素耐受性有关，这使得病原体难以通过常规抗生素疗法根除。铜绿假单胞菌引起的感染引起了极大的关注，特别是对于免疫功能低下和囊性纤维化患者。铜绿假单胞菌凝集素LecA和LecB是毒力因子，在建立生物膜中起关键作用。因此，抑制这些蛋白质的功能具有从保护性生物膜环境中分解细菌和恢复抗生素活性的潜力。在这里，我们报道了基于半乳糖的树状大分子（Gal18）与LecA结合的NMR特征。此外，我们证明了Gal18分子在体外抑制铜绿假单胞菌生物膜形成的活性。