1,3-bis{N^1'-[3'',4''-bis(hydroxy)benzoyl]spermidinyl} citrate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1,3-bis{N^1'-[3'',4''-bis(hydroxy)benzoyl]spermidinyl} citrate
• 英文别名: 1,3-bis-{N1'-[3'',4''-bis(hydroxy)benzoyl]spermidinyl} citrate；1,3-bis-{N1-[3,4-bis(benzyloxy)-benzoyl]-spermidinyl}-citrate；petrobactin；4-[4-[3-[(3,4-dihydroxybenzoyl)amino]propylamino]butylamino]-2-[2-[4-[3-[(3,4-dihydroxybenzoyl)amino]propylamino]butylamino]-2-oxoethyl]-2-hydroxy-4-oxobutanoic acid
• 化学式: C₃₄H₅₀N₆O₁₁
• 分子量: 718.805
• InChiKey: GKIMOVAPSAVJHZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3
• 重原子数：
  51
• 可旋转键数：
  25
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  279
• 氢给体数：
  12
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  1,3-bis{N^1'-[3'',4''-bis(hydroxy)benzoyl]spermidinyl} citrate 在 硼酸 作用下， 以 重水 为溶剂， 生成
  参考文献：
  名称：

  Borate Binding to Siderophores:  Structure and Stability

  摘要：

  \Well-known as specific iron chelating agents produced by bacteria, it is shown that some, but not all, siderophore classes have an unexpected binding affinity for boron. The relevant criterium is the availability of a vicinal dianionic oxygen containing binding group (i.e., citrate or catecholate). The resulting boron complexes have been characterized by ESI-MS, multinuclear NMR, and DFT calculations. Detailed boron binding constants have been measured for vibrioferrin, rhizoferrin, and petrobactin. The observed affinity of certain siderophores for borate, a common chemical species in the marine but not the terrestrial environment, allows for small, but potentially significant, concentrations of B-siderophores to exist at oceanic pH. We hypothesize that these concentrations could be sufficient for them to function as cell signaling molecules or as mediators of biological boron uptake. In addition, binding of the tetrahedral boron to these siderophores results in a conformation that is different from either the free siderophore or its iron complex and would thus allow a distinction to be made between its iron uptake and any putative cell signaling roles.

  DOI：

  10.1021/ja073788v
• 作为产物：
  描述：

  Tert-butyl 4-[4-[3-[[3,4-bis(phenylmethoxy)benzoyl]amino]propylamino]butylamino]-2-[2-[4-[3-[[3,4-bis(phenylmethoxy)benzoyl]amino]propylamino]butylamino]-2-oxoethyl]-2-hydroxy-4-oxobutanoate 在 水 、 三氟乙酸 、 氢气 、 溶剂黄146 、 palladium dichloride 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 4.0h， 生成 1,3-bis{N^1'-[3'',4''-bis(hydroxy)benzoyl]spermidinyl} citrate
  参考文献：
  名称：

  Efficient synthesis of the siderophore petrobactin via antimony triethoxide mediated coupling

  摘要：

  Chemical synthesis of petrobactin, a siderophore for Bacillus anthracis, has been achieved via Sb(OEt)(3)-mediated ester-amide exchange. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2012.01.074

文献信息

• Direct Identification of a Siderophore Import Protein Using Synthetic Petrobactin Ligands
  作者：Nikolas Bugdahn、Florian Peuckert、Alexander G. Albrecht、Marcus Miethke、Mohamed A. Marahiel、Markus Oberthür

  DOI：10.1002/anie.201005527

  日期：2010.12.27

  Nice catch! The immobilization of a synthetic petrobactin derivative on agarose was crucial for the isolation and identification of a bacterial siderophore import protein for the first time from crude cell extracts. The biochemical and genetic characterization of the identified protein confirmed that FpiA (YclQ) is the principal petrobactin importer in Bacillus subtilis.

  好赶上！合成石蜡蛋白衍生物在琼脂糖上的固定对于首次从粗细胞提取物中分离和鉴定细菌铁载体导入蛋白至关重要。鉴定出的蛋白质的生化和遗传学特征证实，FpiA（YclQ）是枯草芽孢杆菌中主要的岩石活化素进口商。
• Syntheses and Iron Binding Affinities of the<i>Bacillus anthracis</i>Siderophore Petrobactin and Sidechain-Modified Analogues
  作者：Nikolas Bugdahn、Markus Oberthür

  DOI：10.1002/ejoc.201301340

  日期：2014.1

  An improved synthesis of petrobactin and analogues has been developed that provides reliable access to siderophores in sufficient quantities for biological studies. The determination of the iron affinity of different petrobactin derivatives showed that functionalization at the central amino group of the spermidine sidechain has only a minor influence on the iron binding properties of the siderophore

  已开发出一种改进的岩杆菌素和类似物的合成方法，可以可靠地获取足够数量的铁载体以进行生物学研究。对不同岩杆菌素衍生物的铁亲和力的测定表明，亚精胺侧链中央氨基的官能化对铁载体的铁结合特性的影响很小。因此，此类衍生物是开发生物探针以研究细菌铁载体转运（抗生素可能的新靶点）的有希望的起点。
• Petrobactin biosynthesis: AsbB catalyzes condensation of spermidine with N8-citryl-spermidine and its N1-(3,4-dihydroxybenzoyl) derivative
  作者：Daniel Oves-Costales、Nadia Kadi、Mark J. Fogg、Lijiang Song、Keith S. Wilson、Gregory L. Challis

  DOI：10.1039/b809353a

  日期：——

  virulence-conferring siderophore petrobactin in Bacillus anthracis, is shown to catalyze efficient ATP-dependent condensation of spermidine, but not N1-(3,4-dihydroxbenzoyl)-spermidine, with N8-citryl-spermidine or N1-(3,4-dihydroxbenzoyl)-N8-citryl-spermidine, suggesting that N1-(3,4-dihydroxbenzoyl)-spermidine is very unlikely to be a significant intermediate in petrobactin biosynthesis, contrary to previous

  AsbB 酶参与炭疽芽孢杆菌中赋予毒力的铁载体岩杆菌素的生物合成，显示可催化亚精胺与 N8- citryl-spermidine 或 N1-(3,4-dihydroxybenzoyl)-N8-citryl-spermidine，表明 N1-(3,4-dihydroxybenzoyl)-spermidine 不太可能是 petrobactin 生物合成中的重要中间体，这与之前的建议相反。
• POLYAMINE TRANSPORT INHIBITORS AS NOVEL THERAPEUTICS
  申请人：Phanstiel Otto

  公开号：US20120172449A1

  公开（公告）日：2012-07-05

  Novel polyamine transport inhibitors have been synthesized and demonstrated to block the uptake of native polyamines into human cancer cells. A combination therapy of the transport inhibitor and DFMO (a drug which blocks polyamine biosynthesis) provided synergistic activity against a metastatic human colon cancer cell line. The strategy uses polyamine depletion and polyamine metabolism to generate reactive oxygen species within cells as a novel way to treat cancers. This approach may be implemented for widespread use in the treatment of diseases which rely upon polyamine transport activity for proliferation.

  新型聚胺运输抑制剂已经合成并证明可以阻止天然聚胺进入人类癌细胞。运输抑制剂和DFMO（一种阻止聚胺生物合成的药物）的联合治疗对转移性人类结肠癌细胞系表现出协同作用。该策略利用聚胺耗竭和聚胺代谢在细胞内产生活性氧自由基的新方法来治疗癌症。这种方法可以在依赖聚胺运输活性进行增殖的疾病的广泛治疗中实施。
• Polyamine transport inhibitors as novel therapeutics
  申请人：Phanstiel Otto

  公开号：US09212131B2

  公开（公告）日：2015-12-15

  Novel polyamine transport inhibitors have been synthesized and demonstrated to block the uptake of native polyamines into human cancer cells. A combination therapy of the transport inhibitor and DFMO (a drug which blocks polyamine biosynthesis) provided synergistic activity against a metastatic human colon cancer cell line. The strategy uses polyamine depletion and polyamine metabolism to generate reactive oxygen species within cells as a novel way to treat cancers. This approach may be implemented for widespread use in the treatment of diseases which rely upon polyamine transport activity for proliferation.

  新型聚胺转运抑制剂已被合成并证明能够阻止原生聚胺进入人类癌细胞。将转运抑制剂与DFMO（一种可阻止聚胺生物合成的药物）结合治疗，在转移性人类结肠癌细胞系中提供了协同作用。该策略利用聚胺耗竭和聚胺代谢产生细胞内活性氧自由基的方式，作为治疗癌症的新方法。这种方法可能被广泛应用于依赖聚胺转运活性进行增殖的疾病的治疗中。