2,3,4,6-tetra-O-acetyl-1-S-mercaptopropionyl-β-D-galactose | 79360-05-7

• 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-tetra-O-acetyl-1-S-mercaptopropionyl-β-D-galactose
• 英文别名: 3-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl-1-thio)propionic acid；1-S-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-3-mercaptopropionate；2,3,4,6-tetra-O-acetylgalactopyranosyl-1-β-(3'-thioropionica acid)；2,3,4,6-tetra-O-acetylgalactopyranosyl-1-β-(3'-thiopropionic acid)；2-Carboxyethyl 2,3,4,6-tetra-O-acetyl-1-thio-β-D-galactopyranoside；peracylated 3-(β-D-galactopyranosylthio)propionic acid；3-[(2,3,4,6-Tetra-O-acetyl-b-D-galactopyranosyl)thio]-propanoic acid；3-[(2S,3R,4S,5S,6R)-3,4,5-triacetyloxy-6-(acetyloxymethyl)oxan-2-yl]sulfanylpropanoic acid
• CAS: 79360-05-7
• 化学式: C₁₇H₂₄O₁₁S
• 分子量: 436.437
• InChiKey: FGMXMRUEYSIRLE-GWFJUFKTSA-N

物化性质

• 沸点：
  544.1±50.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  29
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  177
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  2,3,4,6-tetra-O-acetyl-1-S-mercaptopropionyl-β-D-galactose 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 Acetic acid (2R,3S,4S,5R,6S)-3,5-diacetoxy-2-acetoxymethyl-6-[2-(6-amino-hexylcarbamoyl)-ethylsulfanyl]-tetrahydro-pyran-4-yl ester
  参考文献：
  名称：

  DTPA 双（酰胺）糖缀合物的镧系元素（III）螯合物：靶向无唾液酸糖蛋白受体的潜在成像剂

  摘要：

  合成和表征了一类新的 DTPA 双（酰胺）连接的不同糖类 [乳糖 (Lac) 和半乳糖 (Gal)] 和价态（二和四）及其 LnIII 复合物的糖缀合物的表征。DTPAGal2、DTPAGal4 和 DTPALac2 的 SmIII 和 EuIII 复合物的 1H NMR 谱在 7 到 80°C 之间获得，表明存在由三个结合的 DTPA 氮原子的手性产生的四种可能的非对映异构结构对中的几种在溶液中，具有不同的相对种群。核磁共振谱中中心氮原子外消旋化的动态效应表明，SmIII 配合物在 60°C 时该过程快速，而 EuIII 配合物在 7°C 时缓慢。研究了含有两个乳糖基部分 [GdIII-DTPALac2] 的 GdIII-DTPA 双（酰胺）糖缀合物的水质子的体外 r1 核磁弛豫分散度（NMRD），产生了控制其弛豫性的分子参数。在 25 °C 和 20 MHz 下，其 r1 值比报告的低分子量

  DOI：

  10.1002/ejic.200400766
• 作为产物：
  描述：

  2,3,4,6-四乙酰氧基-alpha-D-吡喃糖溴化物 在 potassium carbonate 作用下， 以 水 、 丙酮 为溶剂， 反应 1.33h， 生成 2,3,4,6-tetra-O-acetyl-1-S-mercaptopropionyl-β-D-galactose
  参考文献：
  名称：

  Design and Synthesis of Bis-Biotin-Containing Reagents for Applications Utilizing Monoclonal Antibody-Based Pretargeting Systems with Streptavidin Mutants

  摘要：

  Previous studies have shown that pretargeting protocols, using cancer-targeting fusion proteins, composed of 4 anti-CD20 single chain Fv (scFv) fragments and streptavidin (scFv(4)-SAv), followed by a biotinylated dendrimeric N-acetyl-galactosamine blood clearing agent (CA), 1, then a radiolabeled DOTA-biotin derivative (a monobiotin), 3a, can provide effective therapy for lymphoma xenografts in mouse models. A shortcoming in this pretargeting system is that endogenous biotin may affect its efficacy in patients. To circumvent this potential problem, we investigated a pretargeting system that employs anti-CD20 scFv(4)-SAv mutant fusion proteins with radioiodinated bis-biotin derivatives. With that combination of reagents, good localization of the radiolabel to lymphoma tumor xenografts was obtained in the presence of endogenous biotin. However, the blood clearance reagents employed in the studies were ineffective, resulting in abnormally high levels of radioactivity in other tissues. Thus, in the present investigation a bis-biotin-trigalactose blood clearance reagent, 2, was designed, synthesized, and evaluated in vivo. Additionally, another DOTA-biotin derivative (a bis-biotin), 4a, was designed and synthesized, such that radiometals (e.g., In-111, Y-90, Lu-177) could be used in the pretargeting protocols employing scFv(4)-SAv mutant fusion proteins. Studies in mice demonstrated that the CA 2 was more effective than CA 1 at removing [I-125]scFv(4)-SAv-S45A mutant fusion proteins from blood. Another in vivo study compared tumor targeting and normal tissue concentrations of the new reagents (2 and [In-111]4b) with standard reagents (1 and [In-111]3b) used in pretargeting protocols. The study showed that lymphoma xenografts could be targeted in the presence of endogenous biotin when anti-CD20 fusion potent containing SAv mutants (scFv(4)-SAv-S45A or scFv(4)-SAv-Y43A) were employed in combination with CA 2 and [In-111]4b). Importantly, normal tissue concentrations of [In-111]4b were similar to those obtained using the standard reagents (1 and [In-111]3b), except that the blood and liver concentrations were slightly higher with the new reagents. While the reasons for the higher blood and liver concentrations are unknown, the differences in the galactose structures of the clearance agents 1 and 2 may play a role.

  DOI：

  10.1021/bc100030q

文献信息

• Use of multivalent glycodendrimers to inhibit the activity of human immunodeficiency virus
  申请人：——

  公开号：US20040180852A1

  公开（公告）日：2004-09-16

  The present invention relates to compositions and methods for inhibiting the interaction of a ligand and receptor. In particular, compositions are methods are provided for inhibition of interaction between a virus, especially HIV, and a receptor. Inhibition of such ligand/receptor interaction is advantageous in inhibiting infection of a cell with a virus. Further, an inhibitor of ligand/receptor interaction serves as a standard in assays of inhibition in vitro or in vivo. In a particular embodiment, a composition according to the invention includes a compound having the formula: [(X)—(Y)] p -Z where X is 1 and where Q1 and Q2 are each independently H, a bond to Y, or a bond to Z, where at least one of Q1 or Q2 is a bond to Y or a bond to Z; where R1, R4, R6 and R8 are each H; R2, R3, and R5 are each independently OH, OSO3D, or OPO3D, and R7 is CH20H, CH2OSO3D or CH2OPO3D; where D is H or a cation selected from the group consisting of: alkali metal cations, alkaline earth metal cations, ammonium cations, quaternary ammonium cations and amine cations; and where at least one of R2, R3, R5 and R7 is a sulfur or phosphate containing group; where Y is an optional linker, Z is a multivalent support, and p is an integer in the range of 1-2000 inclusive.

  本发明涉及用于抑制配体和受体相互作用的组合物和方法。具体而言，提供了用于抑制病毒（特别是HIV）与受体之间相互作用的组合物和方法。抑制此类配体/受体相互作用有助于抑制细胞感染病毒。此外，配体/受体相互作用的抑制剂可作为体外或体内抑制测定的标准。在一个特定实施例中，根据本发明的组合物包括具有以下结构的化合物：[(X)—(Y)] p -Z，其中X为1，Q1和Q2分别独立地为H、与Y的键或与Z的键，其中Q1或Q2中至少有一个是与Y的键或与Z的键；R1、R4、R6和R8各自为H；R2、R3和R5各自独立地为OH、OSO3D或OPO3D，R7为 0H、CH2OSO3D或 OPO3D；D为H或从以下群组中选择的阳离子：碱金属阳离子、碱土金属阳离子、铵阳离子、季铵阳离子和胺阳离子；其中R2、R3、R5和R7中至少有一个是含硫或磷酸酯基团；Y为可选的连接剂，Z为多价支持体，p为在1-2000范围内的整数。
• Lanthanide(<scp>III</scp>) Complexes of DOTA-Glycoconjugates: A Potential New Class of Lectin-Mediated Medical Imaging Agents
  作者：João P. André、Carlos F. G. C. Geraldes、José A. Martins、André E. Merbach、Maria I. M. Prata、Ana C. Santos、João J. P. de Lima、Éva Tóth

  DOI：10.1002/chem.200400187

  日期：2004.11.19

  The synthesis and characterization of a new class of DOTA (1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane) monoamide-linked glycoconjugates (glucose, lactose and galactose) of different valencies (mono, di and tetra) and their Sm(III), Eu(III) and Gd(III) complexes are reported. The 1H NMR spectrum of Eu(III)-DOTALac2 shows the predominance of a single structural isomer of square antiprismatic

  新型DOTA（1,4,7,10-四（羧甲基）-1,4,7,10-四氮杂环十二烷）单酰胺连接的糖价（葡萄糖，乳糖和半乳糖）连接的糖共轭物的合成与表征，二和四）及其Sm（III），Eu（III）和Gd（III）配合物。Eu（III）-DOTALac2的1H NMR谱图显示了DOTA螯合部分的方形反棱角几何结构的单个结构异构体的优势，并且绕着与靶向糖树状聚合物连接的酰胺键快速旋转。通过1H核磁弛豫分散液（NMRD）研究了Gd（III）-糖基共轭物的体外弛豫性，得出的参数接近于其他DOTA单酰胺所报道的参数。
• Building blocks for glycopeptide synthesis: glycosylation of 3-mercaptopropionic acid and Fmoc amino acids with unprotected carboxyl groups
  作者：Mikael Elofsson、Björn Walse、Jan Kihlberg

  DOI：10.1016/0040-4039(91)80548-k

  日期：1991.12

  3-Mercaptopropionic acid and Fmoc amino acids, having unprotected carboxyl groups, were glycosylated with sugar 1,2-trans-acetates in 90 and 53–65% yields, respectively, under Lewis acid promotion. The synthesis of a neoglycopeptide illustrates the use of the building blocks in solid phase peptide synthesis.

  在路易斯酸的促进下，将具有未保护羧基的3-巯基丙酸和Fmoc氨基酸分别与糖1,2-反式乙酸酯进行糖基化处理，产率分别为90％和53-65％。新糖肽的合成说明了结构单元在固相肽合成中的用途。
• Synthesis, Biological Evaluation, WAC and NMR Studies of<i>S</i>-Galactosides and Non-Carbohydrate Ligands of Cholera Toxin Based on Polyhydroxyalkylfuroate Moieties
  作者：Javier Ramos-Soriano、Ulf Niss、Jesús Angulo、Manuel Angulo、Antonio J. Moreno-Vargas、Ana T. Carmona、Sten Ohlson、Inmaculada Robina

  DOI：10.1002/chem.201302786

  日期：2013.12.23

  The synthesis of several non‐carbohydrate ligands of cholera toxin based on polyhydroxyalkylfuroate moieties is reported. Some of them have been linked to D‐galactose through a stable and well‐tolerated S‐glycosidic bond. They represent a novel type of non‐hydrolyzable bidentate ligand featuring galactose and polyhydroxyalkylfuroic esters as pharmacophoric residues, thus mimicking the GM1 ganglioside

  报道了基于聚羟烷基糠酸酯部分的几种霍乱毒素的非碳水化合物配体的合成。其中一些已通过稳定且耐受良好的S与D-半乳糖相连糖苷键。它们代表了一种新型的不可水解的二齿配体，其特征在于半乳糖和聚羟烷基糠酸酯为药效基团残基，从而模仿了GM1神经节苷脂。通过弱亲和色谱法（WAC）测量了新化合物对霍乱毒素的亲和力。还通过饱和转移差异NMR实验研究了最佳候选物与该毒素的相互作用，该实验可以鉴定与蛋白质相互作用的配体的结合表位。有趣的是，基于聚羟烷基糠酸酯结构的非碳水化合物模拟物显示出最高的亲和力。
• Synthesis of Cell-Penetrating<i>S</i>-Galactosyl-Oligoarginine Peptides as Inducers of Recombinant Protein Expression under the Control of<i>lac</i>Operator/Repressor Systems
  作者：Yukina Mizuta、Akinori Takasu、Masahiro Higuchi

  DOI：10.1002/cplu.201300130

  日期：2013.7

  The synthesis of glycodendrimers and glycopoly(oxazoline)s as inducers of recombinant protein expression has recently been reported; however, these compounds induced the expression of only small amounts of the green fluorescence protein (GFP), which was used as the model recombinant protein, because of their poor ability to penetrate the Escherichia coli cell membrane. Therefore, S-galactosyl-oligo(Arg)

  最近报道了糖树状大分子和糖多（恶唑啉）的合成作为重组蛋白表达的诱导剂。然而，由于这些化合物穿透大肠杆菌细胞膜的能力较弱，因此它们仅诱导了少量的绿色荧光蛋白（GFP）的表达，并将其用作模型重组蛋白。因此，现在已经合成了S-半乳糖基-寡（Arg）缀合物来克服这个问题。在大肠杆菌中的T5启动子上，每个S-半乳糖基（Arg）n构建体（n = 5、6、8）诱导的GFP在大肠杆菌中表达18小时后，我们目视观察到培养物发出绿色荧光。用紫外线激发。这些培养物的荧光强度大于对照培养物的荧光强度，这表明该肽已经诱导了GFP表达。定量荧光测量也支持以下观察：与半乳糖基树状大分子，聚（恶唑啉）和天然诱导剂乳糖相比，该肽是更好的GFP表达诱导剂。因为GFP的表达水平与每个肽中的精氨酸部分的数量直接相关，所以我们建议精氨酸部分的数量决定每个肽通过大肠杆菌膜的能力，从而影响表达水平。当将T7启动子置于人工细胞外基质蛋白