α-folate-NHS | 544429-89-2

• 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: α-folate-NHS
• CAS: 544429-89-2
• 化学式: C₂₃H₂₂N₈O₈
• 分子量: 538.476
• InChiKey: PNWGIHRMRJNSGU-AWEZNQCLSA-N

物化性质

• 密度：
  1.72±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.52
• 重原子数：
  39.0
• 可旋转键数：
  10.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  239.66
• 氢给体数：
  5.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  α-folate-NHS 、 、 NAlpha-BOC-Nε-FMOC-L-赖氨酸 、 Fmoc-Lys(Dde)-OH 、 1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸四叔丁酯 在 4-二甲氨基吡啶 、 N,N'-二异丙基碳二亚胺 、 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.75h， 生成
  参考文献：
  名称：

  一种与叶酸受体靶向结合的叶酸二聚体复合 物及其应用

  摘要：

  本发明属于医学领域，公开了一种与叶酸受体靶向结合的叶酸二聚体复合物及其应用。该复合物为X2‑Y‑Z‑A，其中：X2为赖氨酸连接叶酸的二聚体或赖氨酸连接叶酸衍生物的二聚体；Y为具有“(聚乙二醇或聚乙二醇类衍生物)m‑赖氨酸”结构的偶联物，m＝1，2，3，4，5；Z为DOTA、NOTA、CB‑TE2A、DTPA、NODAGA等物质及它们的衍生物；A为放射性核素、磁共振显像剂、化学药物、或者荷载化学药物的纳米粒子；X，Y，Z和A各单元之间以共价键相连。该复合物可用于制备肿瘤靶向显像和治疗的药物，能有效提高放射性核素在肿瘤及其转移灶的聚集，提高诊断效能和治疗效果。

  公开号：

  CN104815336B
• 作为产物：
  描述：

  N-羟基丁二酰亚胺 、 folate 在 carbodiimide reagent 作用下， 以 二甲基亚砜 为溶剂， 反应 12.0h， 生成 α-folate-NHS
  参考文献：
  名称：

  使用柠檬酸柠檬汁和共轭表柔比星的水性水果提取物超快合成稳定的金纳米颗粒：靶向药物的治疗，用于治疗乳腺癌†

  摘要：

  在这项研究中，绿色化学方法被用于通过使用柠檬酸柠檬的水果提取物快速合成金纳米颗粒（AuNPs）（在30秒内）。该研究的重点是在没有柠檬酸的情况下形成酸稳定的L. AuNPs。使用任何催化剂。AuNPs的合成通过观察537 nm的表面等离振子共振（SPR）谱带得以确认。在这些加盖的AuNPs的表面上，表柔比星（EPI）与活化的叶酸（FA）结合在一起，用于靶向药物递送。使用FTIR和紫外可见分光光度计对EPI–FA–AuNPs复合物进行表征，并通过HR-TEM，粒度分析仪和Zeta电位测量对AuNPs进行表征。体外稳定性实验表明，AuNPs在生理条件下是稳定的。在体外自由EPI和EPI-FA-的AuNP的细胞毒性进行了研究针对MCF-7细胞，结果表明，EPI-FA-的AuNP的50％就足以实现生长的抑制（IC 50），并且所述量为低于免费的EPI。流式细胞仪分析显示，用EPI–FA–AuNPs处理后，G

  DOI：

  10.1039/c6ra01482h

文献信息

• TARGETING MICROBUBBLES
  申请人：CALIFORNIA INSTITUTE OF TECHNOLOGY

  公开号：US20160367669A1

  公开（公告）日：2016-12-22

  This invention related to manufactured microbubbles, as well as methods of using manufactured microbubbles, for example, in medicinal applications. The invention pertains to the physical structure and materials of the microbubbles, as well as to methods for manufacturing microbubbles, methods for targeting microbubbles for specific medicinal applications, and methods for delivering microbubbles in medical treatment.

  这项发明涉及制造微泡，以及使用制造的微泡的方法，例如在药用应用中。该发明涉及微泡的物理结构和材料，以及制造微泡的方法，将微泡定位到特定药用应用的方法，以及在医疗治疗中输送微泡的方法。
• Folate-Cyclodextrin Conjugates as Carriers of the Platinum(IV) Complex LA-12
  作者：Valentina Giglio、Valentina Oliveri、Maurizio Viale、Rosaria Gangemi、Giovanni Natile、Francesco P. Intini、Graziella Vecchio

  DOI：10.1002/cplu.201402342

  日期：2015.3

  characterised. As a proof of concept, the antitumour platinum(IV) complex cis-trans-cis-[PtCl2 (CH3 CO2 )2 (adamantylamine)(NH3 )] (LA-12) has been used as a guest drug. The LA-12-cyclodextrin inclusion complexes have been tested on tumour cells. In the presence of cyclodextrin-folate conjugates, LA-12 exhibited IC50 values four times smaller than those of LA-12 alone in MDA-MB-231 cells, which overexpress

  叶酸已成为一种有趣的细胞靶向部分，许多药物已与叶酸结合。在这种情况下，已经合成了β-环糊精与叶酸的新缀合物作为药物载体，以提高其对过表达叶酸受体的细胞的选择性。特别地，已经合成并充分表征了与叶酸的α-或γ-羧基连接的3-和6-官能化的β-环糊精。作为概念的证明，抗肿瘤铂（IV）复合物顺-反-顺-[PtCl2（CH3 CO2）2（金刚烷基胺）（NH3）]（LA-12）已用作客用药物。LA-12-环糊精包合物已经在肿瘤细胞上进行了测试。在存在环糊精-叶酸结合物的情况下，LA-12在MDA-MB-231细胞中的IC50值比单独的LA-12小四倍。在其膜上过表达叶酸受体。在未过度表达叶酸受体的对照肿瘤细胞中未发现LA-12细胞毒性的改善。因此，基于具有功能化环糊精的包合物的非共价方法，对于靶向药物而言似乎非常有前途。
• A step-wise synthetic approach is necessary to access γ-conjugates of folate: folate-conjugated prodigiosenes
  作者：Carlotta Figliola、Estelle Marchal、Brandon R. Groves、Alison Thompson

  DOI：10.1039/c9ra01435g

  日期：——

  Despite the vast literature that describes reacting folic acid with a pharmacophore, this route is ineffective in providing the correct regioisomer of the resulting conjugate.

  尽管有大量的文献描述了将叶酸与药效团反应，但这种方法无法有效地提供所需的共轭物的正确位置异构体。
• WO2006/73419
  申请人：——

  公开号：——

  公开（公告）日：——
• Multifunctional DNA-Gold Nanoparticles for Targeted Doxorubicin Delivery
  作者：Colleen M. Alexander、Kristen L. Hamner、Mathew M. Maye、James C. Dabrowiak

  DOI：10.1021/bc500136r

  日期：2014.7.16

  In this report we describe the synthesis, characterization, and cytotoxic properties of DNA-capped gold nanoparticles having attached folic acid (FA), a therrnoresponsive polymer (p), and/or poly(ethylene glycol) (PEG) oligomers that could be used to deliver the anticancer drug doxorubicin (DOX) in chemotherapy. The FA-DNA oligomer used in the construction of the delivery vehicle was synthesized through the reaction of the isolated folic acid N-hydroxysuccinimide ester with the amino-DNA and the conjugated DNA product was purified using high performance liquid chromatography (HPLC). This approach ultimately allowed control of the amount of FA attached to the surface of the delivery vehicle. Cytotoxicity studies using SK-N-SH neuroblastoma cells with drug loaded delivery vehicles were carried out using a variety of exposure times (1-48 h) and recovery times (1-72 h), and in order to access the effects of varying amounts of attached FA, in culture media deficient in FA. DOX loaded delivery vehicles having 50% of the DNA strands with attached FA were more cytotcodc than when all of the strands contained FA. Since FA stimulates cell growth, the reduced cytotoxicity of vehicles fully covered with FA suggests that the stimulatory effects of FA can more than compensate for the cytotoxic effects of the drug on the cell population. While attachment of hexa-ethylene glycol PEG(18) to the surface of the delivery vehicle had no effect on c-ytotoxicity, 100% FA plus the thermoresponsive polymer resulted in IC50 = 0.48 +/- 0.01 for an exposure time of 24 h and a recovery time of 1 h, which is an order of magnitude more cytotoxic than free DOX. Confocal microscopic studies using fluorescence detection showed that SK-N-SH neuroblastoma cells exposed to DOX-loaded vehicles have drug accumulation inside the cell and, in the case of vehicles with attached FA and thermoresponsive polymer, the drug appears more concentrated. Since the biological target of DOX is DNA, the latter observation is consistent with the high cytotoxicity of vehicles having both FA and the thermoresponsive polymer. The study highlights the potential of DNA-capped gold nanoparticles as delivery vehicles for doxorubicin in cancer chemotherapy.