2-(2-amino-3-phenylpropanamido)-N-(naphthalen-2-yl)-5-guanidinopentanamide

• 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-(2-amino-3-phenylpropanamido)-N-(naphthalen-2-yl)-5-guanidinopentanamide
• 英文别名: L-phenylalanyl-L-arginine β-naphthylamide；L-phenylalanyl-L-arginyl-β-naphthylamide；phenylalanine arginine β-naphthylamide；phenylalanine-arginine β-naphthylamide；phenylalanine-arginine-β-naphthylamide；phenylalanine-arginyl β-naphthylamide；N2-(L-Phenylalanyl)-N1-(naphthalenyl)-L-arigninamide；(2S)-2-[[(2S)-2-amino-3-phenylpropanoyl]amino]-5-(diaminomethylideneamino)-N-naphthalen-2-ylpentanamide
• 化学式: C₂₅H₃₀N₆O₂
• 分子量: 446.552
• InChiKey: ZNHUFUZDUQRKBB-VXKWHMMOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  149
• 氢给体数：
  5
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(2-amino-3-phenylpropanamido)-N-(naphthalen-2-yl)-5-guanidinopentanamide 在 human dipeptidyl peptidase III, a metallopeptidase of the M₄₉ family 作用下， 以 aq. buffer 为溶剂， 生成 2-萘胺
  参考文献：
  名称：

  Hydrolysis of dipeptide derivatives reveals the diversity in the M49 family

  摘要：

  二肽酶III是M49家族的金属肽酶，最初在垂体中通过特定的二精氨酰芳胺裂解而被识别出来，这些芳胺一直被用作首选的测定底物。在这里，我们同时检测了酵母和人类二肽酶III的活性。人类酶更喜欢Arg₂-β-萘胺，并显示出这种底物的620倍高的k_cat/K_m。相比之下，酵母酶对分析的任何X-Arg-β-萘胺都没有显示出偏好。用Asp取代Gly⁵⁰⁵导致酵母酶形成了一个活性较低但更具选择性的形式。这些结果表明M49家族的裂解特异性存在多样性。

  DOI：

  10.1515/hsz-2012-0347
• 作为产物：
  描述：

  2-(2-tert-butoxycarbonylamino-2-benzylethylamido)-N-(naphthalen-2-yl)-5-guanidinopentanamide 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以25%的产率得到2-(2-amino-3-phenylpropanamido)-N-(naphthalen-2-yl)-5-guanidinopentanamide
  参考文献：
  名称：

  Evaluation of the Efficiency of Synthesized Efflux Pump Inhibitors onSalmonella entericaser. Typhimurium Cells

  摘要：

  Multidrug efflux pump inhibitors have a great potential as pharmacological agents that increase the drug susceptibility of bacterial pathogens. Our study was focused on the synthesis and evaluation of the efficiency of resistance–nodulation–division (RND) family efflux pump inhibitors. The efficiency of these inhibitors was investigated on Salmonella enterica ser. typhimurium cells using tetraphenylphosphonium (TPP+) and ethidium cations as the efflux pump substrates. Results of our study indicated that efficiency of the inhibitors depends on the cell outer membrane permeability and method of the assay used. Temperature of the incubation medium and a solvent of the inhibitor used have only minor effect on results of the assay.

  DOI：

  10.1111/cbdd.12173

文献信息

• Conjugation of a New Series of Dithiocarbazate Schiff Base Copper(II) Complexes with Vectors Selected to Enhance Antibacterial Activity
  作者：May Lee Low、Laure Maigre、Pierre Dorlet、Régis Guillot、Jean-Marie Pagès、Karen A. Crouse、Clotilde Policar、Nicolas Delsuc

  DOI：10.1021/bc5004907

  日期：2014.12.17

  with methyl levulinate (SMML, SBML), levulinic acid (SMLA, SBLA), and 4-carboxybenzaldehyde (SM4CB, SB4CB) were reacted with copper(II), producing complexes of general formula ML2 (M = Cu(II), L = ligand). All compounds were characterized using established physicochemical and spectroscopic methods. Crystal structures were determined for three Schiff bases (SMML, SBML, SBLA) and two Cu(II) complexes

  由S-甲基二硫代氨基甲酸酯（SMDTC）和S-苄基二硫代氨基甲酸酯（SBDTC）与乙酰丙酸甲酯（SMML，SBML），乙酰丙酸（SMLA，SBLA）和4-羧基苯甲醛（SM4CB，SB4CB）衍生的一系列六个席夫碱新反应与铜（II）生成通式ML 2（M = Cu（II），L =配体）的配合物。所有化合物均使用已建立的物理化学和光谱方法进行了表征。确定了三个席夫碱（SMML，SBML，SBLA）和两个Cu（II）配合物（Cu（SMML）2和Cu（SMLA）2的晶体结构）。为了提供对络合物在溶液中行为的更多了解，进行了电子顺磁共振（EPR）和电化学实验。母体配体及其各自的铜（II）配合物对革兰氏阴性菌和革兰氏阳性菌均表现出中等的抗菌活性。活性最高的配体（SB4CB）及其类似的S-甲基衍生物（SM4CB）与各种载体部分缀合：聚精氨酸（R1，R4，R9和RW9），低聚乙二醇（OEG）和外排泵阻滞剂苯
• Antimicrobial Compounds and Formulations
  申请人：Svendsen John Sigurd

  公开号：US20120108520A1

  公开（公告）日：2012-05-03

  The invention relates to the use of a molecule comprising a backbone of 2 to 35 non-hydrogen atoms in length, having covalently attached thereto at least two bulky and lipophilic groups and having at least one more cationic than anionic moiety, in the manufacture of a medicament for destabilising microbial cell membranes and the use as a membrane acting antimicrobial agent of a molecule comprising a backbone of 2 to 35 non-hydrogen atoms in length, having covalently attached thereto a super bulky and lipophilic group comprising at least 9 non-hydrogen atoms and having at least two more cationic than anionic moieties and to methods of treatment involving such molecules, in particular peptides including peptide derivatives, and peptidomimetics.

  本发明涉及使用一种分子，其包含长度为2至35个非氢原子的骨架，并且至少连接有两个笨重和亲脂性基团，并且具有至少一个阳离子大于阴离子的基团，在制造破坏微生物细胞膜的药物方面使用该分子。另外，本发明还涉及使用一种分子作为膜作用抗微生物剂，该分子包括长度为2至35个非氢原子的骨架，并且共价连接有一个超大的、亲脂性的基团，包括至少9个非氢原子，并且具有至少两个阳离子大于阴离子的基团。本发明还涉及涉及这样的分子的治疗方法，特别是包括肽衍生物和肽类似物的肽。
• DEVICE AND METHOD FOR SOLUBILIZING, SEPARATING, REMOVING AND REACTING CARBOXYLIC ACIDS IN OILS, FATS, AQUEOUS OR ORGANIC SOLUTIONS BY MEANS OF MICRO-OR NANOEMULSIFICATION
  申请人：Dietz Ulrich

  公开号：US20130090488A1

  公开（公告）日：2013-04-11

  The present invention is directed to solubilizing compounds, a device and a method for solubilizing and removing carboxylic acids and especially fatty acids from oils, fats, aqueous emulsion, aqueous media and organic solutions. Devices utilizing the inventive method shall be used for separating carboxylic acids from oils, fats, aqueous emulsion, lipophilic media or organic solutions, respectively by preparing an aqueous micro- or nanoemulsion of the carboxylic acids especially the fatty acids and the solubilizing compound which contains at least one amidino and/or gianidino group. Solubilization effects of solubilizing compounds combined with the inventive use of separation methods for carboxylic acids can be used to treat persons in need of removal of fatty acids or analyze carboxylic acids from blood or process other solutions in food, pharmacy, chemistry, bio fuel industry or other industrial processings.

  本发明涉及溶解化合物、用于从油、脂肪、水乳液、水介质和有机溶液中溶解和去除羧酸，特别是脂肪酸的装置和方法。采用本发明方法的装置将用于通过制备羧酸特别是脂肪酸和含有至少一种氨基甲酰基和/或肼基团的溶解化合物的水微观或纳米乳液，分离油、脂肪、水乳液、亲脂性介质或有机溶液中的羧酸。溶解化合物的溶解效果与本发明所述的羧酸分离方法相结合，可用于治疗需要去除脂肪酸或从血液中分析羧酸或处理食品、药品、化学、生物燃料工业或其他工业加工过程中的其他溶液的人员。
• Device and method for solubilizing, separating, removing and reacting carboxylic acids in oils, fats, aqueous or organic solutions by means of micro-or nanoemulsification
  申请人：Dietz Ulrich

  公开号：US09127233B2

  公开（公告）日：2015-09-08

  The present invention is directed to solubilizing compounds, a device and a method for solubilizing and removing carboxylic acids and especially fatty acids from oils, fats, aqueous emulsion, aqueous media and organic solutions. Devices utilizing the inventive method shall be used for separating carboxylic acids from oils, fats, aqueous emulsion, lipophilic media or organic solutions, respectively by preparing an aqueous micro- or nanoemulsion of the carboxylic acids especially the fatty acids and the solubilizing compound which contains at least one amidino and/or gianidino group. Solubilization effects of solubilizing compounds combined with the inventive use of separation methods for carboxylic acids can be used to treat persons in need of removal of fatty acids or analyze carboxylic acids from blood or process other solutions in food, pharmacy, chemistry, bio fuel industry or other industrial processings.

  本发明涉及可溶化化合物、用于从油、脂肪、水乳液、水介质和有机溶液中溶解和去除羧酸，特别是脂肪酸的装置和方法。采用本发明方法的装置将用于通过制备羧酸，特别是脂肪酸和含有至少一种酰胺基和/或氨基甲酸基团的可溶化化合物的水微观或纳米乳液，分离油、脂肪、水乳液、亲脂性介质或有机溶液中的羧酸。可溶化化合物的溶解效果与本发明用于羧酸的分离方法相结合，可用于治疗需要去除脂肪酸或分析血液中的羧酸或处理食品、药品、化学品、生物燃料工业或其他工业加工中的其他溶液的人。
• Scalable and Chromatography‐Free Synthesis of Efflux Pump Inhibitor Phenylalanine Arginine β‐Naphthylamide for Its Validation in Wild‐Type Bacterial Strains
  作者：Christopher M. Russo、Kelsey G. Howey、Matthew C. O'Reilly

  DOI：10.1002/cmdc.202300128

  日期：2023.7.17

  Phenylalanine arginine β‐naphthylamine, or PAβN, is a C‐terminus capped dipeptide discovered in 1999 as an RND‐type efflux pump inhibitor (EPI). Since then, PAβN has become a standard tool compound in EPI research and development. Despite this, PAβN lacks a detailed or efficient synthesis, and standard parameters for its use in wild‐type bacterial strains are inconsistent or non‐existent. Therefore, a scalable and chromatography‐free synthesis of PAβN was developed using streamlined traditional solution‐phase peptide coupling chemistry. With this procedure, gram scale quantities of PAβN were synthesized alongside analogues and stereoisomers to build a focused library to evaluate simple structure activity relationships. While most analogues were less active than the broadly utilized L,L‐PAβN itself, we identified that its enantiomer, D,D‐PAβN, also provided 8‐ to 16‐fold potentiation of the antibiotic levofloxacin at 40 to 50 μg/mL concentrations of EPI in various wild‐type Pseudomonas aeruginosa strains. Additionally, D,D‐PAβN was shown to be significantly more hydrolytically stable than L,L‐PAβN, indicating that it may be a useful, and now readily synthesized, tool compound facilitating future EPI research.

  摘要 苯丙氨酸精氨酸 β-萘胺（或 PAβN）是一种 C 端封端二肽，于 1999 年作为 RND 型外排泵抑制剂（EPI）被发现。从那时起，PAβN 已成为 EPI 研究和开发的标准工具化合物。尽管如此，PAβN 仍然缺乏详细或高效的合成方法，在野生型细菌菌株中使用的标准参数也不一致或不存在。因此，我们利用简化的传统溶液相多肽偶联化学方法，开发了一种可扩展的无色谱法合成 PAβN。通过这种方法，我们合成了克级数量的 PAβN，同时还合成了类似物和立体异构体，从而建立了一个重点库，用于评估简单的结构活性关系。虽然大多数类似物的活性低于广泛使用的 L,L-PAβN，但我们发现其对映体 D,D-PAβN，在各种野生型铜绿假单胞菌菌株中，当 EPI 浓度为 40 至 50 μg/mL 时，也能使抗生素左氧氟沙星的药效增强 8 至 16 倍。此外，D,D-PAβN 的水解稳定性明显高于 L,L-PAβN，这表明它可能是一种有用的工具化合物，而且现在很容易合成，有助于未来的 EPI 研究。