N-methacryl arginine | 273921-75-8

• 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: N-methacryl arginine
• 英文别名: methacryloylarginine；N-methacryl-arginine；(2S)-5-(diaminomethylideneamino)-2-(2-methylprop-2-enoylamino)pentanoic acid
• CAS: 273921-75-8
• 化学式: C₁₀H₁₈N₄O₃
• 分子量: 242.278
• InChiKey: GPYHREJCUKUAMM-ZETCQYMHSA-N

物化性质

• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  131
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-methacryl arginine 、 在 三(2-吡啶基甲基)胺 、 copper(I) bromide 、 维生素 C 作用下， 以 二甲基亚砜 为溶剂， 反应 12.0h， 生成
  参考文献：
  名称：

  Star-Like Oligo-Arginyl-Maltotriosyl Derivatives as Novel Cell-Penetrating Enhancers for the Intracellular Delivery of Colloidal Therapeutic Systems

  摘要：

  A novel nonpeptide, multiarmed oligo-arginyl derivative was engineered as a cell-penetration enhancer for the delivery of bioactive macromolecules and colloidal drug systems. Hepta-arginyl-maltotriosylamido-N-acetyl-dodecanoyl acid (Arg(7)-Malt-NAcC12 acid) was synthesized through a carefully designed multistep chemical protocol, as follows: (1) maltotriose derivatization with 12-amino-dodecanoic acid and acetylation of the free amino group; (2) esterification of the maltotriosyl hydroxyl groups with 2-bromo-isobutyryl bromide; and (3) synthesis of star like oligomer bearing multiple copies of arginine moieties under atom transfer radical polymerization (ATRP) conditions. The intermediates and final product were characterized by H-1 NMR, IR, mass spectrometry, colorimetric assays, and elemental analysis. Cytotoxicity studies on the final polymeric material showed that this novel cell penetrating enhancer does not have significant toxic effects on MCF-7 and MC3T3-E1 cell lines. The IC50 was greater than 100 mu M with both cell lines, while the polyethylenimine with similar average molecular mass (M-n) that was used as a reference showed an IC50 of 30 and 40 mu M, for MCF-7 and MC3T3-E1, respectively. The biological properties of the novel bioconjugate were investigated using a fluorescein labeled bovine serum albumin (FITC-BSA) as a hydrophilic cargo model. MCF-7 and MC3T3-E1 cells were incubated for 60 min with the Arg(7)-Malt-NAcC12-conjugated FITC-BSA [(Arg(7)-Malt-NAcC12)(2)-FITC-BSA] or FITC-BSA, and the intracellular fluorescence level was analyzed by spectrofluorimetric analysis of cell lysate, cytofluorimetry, and confocal microscopy. The fluorescence of the lysate of MCF-7 and MC3T3-E1 cells that were incubated with (Arg(7)-Malt-NAcC12)(2)-FITC-BSA at 37 degrees C was approximately 4.5 times higher than the fluorescence obtained with cells incubated with FITC-BSA. At 4 degrees C, the cell uptake of (Arg(7)-Malt-NAcC12)(2)-FITC-BSA was only 2 times higher than that of FITC-BSA. Cytofluorimetric studies showed that, after (Arg(7)-Malt-NAcC12)(2)-FITC-BSA treatment, over 80% of MCF-7 cells and over 95% of MC3T3-E1 cells displayed enhanced fluorescence. Confocal investigations showed punctuated fluorescence within the cytosol in both cell lines, indicating that (Arg(7)-Malt-NAcC12)(2)-FITC-BSA was confined to endosomes, with no fluorescence observed in the nucleus.

  DOI：

  10.1021/bc200666u
• 作为产物：
  描述：

  L-精氨酸盐酸盐 、 甲基丙烯酰氯 在 碳酸氢钠 、 盐酸 作用下， 以 水 为溶剂， 反应 1.0h， 以2.4 g的产率得到N-methacryl arginine
  参考文献：
  名称：

  Star-Like Oligo-Arginyl-Maltotriosyl Derivatives as Novel Cell-Penetrating Enhancers for the Intracellular Delivery of Colloidal Therapeutic Systems

  摘要：

  A novel nonpeptide, multiarmed oligo-arginyl derivative was engineered as a cell-penetration enhancer for the delivery of bioactive macromolecules and colloidal drug systems. Hepta-arginyl-maltotriosylamido-N-acetyl-dodecanoyl acid (Arg(7)-Malt-NAcC12 acid) was synthesized through a carefully designed multistep chemical protocol, as follows: (1) maltotriose derivatization with 12-amino-dodecanoic acid and acetylation of the free amino group; (2) esterification of the maltotriosyl hydroxyl groups with 2-bromo-isobutyryl bromide; and (3) synthesis of star like oligomer bearing multiple copies of arginine moieties under atom transfer radical polymerization (ATRP) conditions. The intermediates and final product were characterized by H-1 NMR, IR, mass spectrometry, colorimetric assays, and elemental analysis. Cytotoxicity studies on the final polymeric material showed that this novel cell penetrating enhancer does not have significant toxic effects on MCF-7 and MC3T3-E1 cell lines. The IC50 was greater than 100 mu M with both cell lines, while the polyethylenimine with similar average molecular mass (M-n) that was used as a reference showed an IC50 of 30 and 40 mu M, for MCF-7 and MC3T3-E1, respectively. The biological properties of the novel bioconjugate were investigated using a fluorescein labeled bovine serum albumin (FITC-BSA) as a hydrophilic cargo model. MCF-7 and MC3T3-E1 cells were incubated for 60 min with the Arg(7)-Malt-NAcC12-conjugated FITC-BSA [(Arg(7)-Malt-NAcC12)(2)-FITC-BSA] or FITC-BSA, and the intracellular fluorescence level was analyzed by spectrofluorimetric analysis of cell lysate, cytofluorimetry, and confocal microscopy. The fluorescence of the lysate of MCF-7 and MC3T3-E1 cells that were incubated with (Arg(7)-Malt-NAcC12)(2)-FITC-BSA at 37 degrees C was approximately 4.5 times higher than the fluorescence obtained with cells incubated with FITC-BSA. At 4 degrees C, the cell uptake of (Arg(7)-Malt-NAcC12)(2)-FITC-BSA was only 2 times higher than that of FITC-BSA. Cytofluorimetric studies showed that, after (Arg(7)-Malt-NAcC12)(2)-FITC-BSA treatment, over 80% of MCF-7 cells and over 95% of MC3T3-E1 cells displayed enhanced fluorescence. Confocal investigations showed punctuated fluorescence within the cytosol in both cell lines, indicating that (Arg(7)-Malt-NAcC12)(2)-FITC-BSA was confined to endosomes, with no fluorescence observed in the nucleus.

  DOI：

  10.1021/bc200666u

文献信息

• [EN] CORONA-LIKE (GUANIDYL)-OLIGOSACCHARIDIC DERIVATIVES AS CELL-PENETRATING ENHANCERS FOR INTRACELLULAR DELIVERY OF COLLOIDAL THERAPEUTIC SYSTEMS<br/>[FR] DÉRIVÉS (GUANIDYL)-OLIGOSACCHARIDIQUES DE TYPE COURONNE EN TANT QU'AMÉLIORATEURS DE LA PÉNÉTRATION CELLULAIRE POUR L'ADMINISTRATION INTRACELLULAIRE DE SYSTÈMES THÉRAPEUTIQUES COLLOÏDAUX
  申请人：UNIV PADOVA

  公开号：WO2012097876A1

  公开（公告）日：2012-07-26

  A novel class of cell-penetrating enhancers with unusual chemical structure is herein disclosed. Said cell-penetrating enhancers are non-linear and non peptidic (guanidyl)-oligosaccharidic derivatives, which can be easily obtained according to simple and reproducible synthetic steps. A wide array of cell penetration enhancers can be obtained by slight modification of the main structure oligosaccharidic backbone and in order to provide for their conjugation or physical combination with a variety of therapeutic systems. These molecules can be designed for conjugation to proteins or polymer therapeutics or for surface decoration of liposomes or nanoparticles. Finally, the cationic features and the penetration enhancer properties of the corona-like (guanidyl)-oligosaccharidic derivatives can be exploited for oligonucleotide, namely siRNA, or gene delivery.

  本文披露了一种新型的细胞穿透增强剂，其化学结构不同寻常。这些细胞穿透增强剂是非线性和非肽的（鸟氨酸）-寡糖衍生物，可以通过简单可重复的合成步骤轻松获得。通过略微修改主要结构寡糖骨架，可以获得各种细胞穿透增强剂，以便与各种治疗系统进行结合或物理组合。这些分子可以设计用于与蛋白质或聚合物治疗系统结合，或用于脂质体或纳米粒子的表面装饰。最后，这种类似冠状的（鸟氨酸）-寡糖衍生物的阳离子特性和穿透增强剂特性可以用于寡核苷酸，即siRNA或基因传递。
• AMINO ACID-BASED POLYMERIZABLE COMPOUNDS AND OPHTHALMIC DEVICES PREPARED THEREFROM
  申请人：Johnson & Johnson Vision Care, Inc.

  公开号：US20210388142A1

  公开（公告）日：2021-12-16

  Provided are amino acid based polymerizable compounds and their applications in ophthalmic devices. The amino acid based polymerizable compounds are of formula I: wherein R, R 1 , and R 2 are as described herein.

  提供了基于氨基酸的可聚合化合物及其在眼科设备中的应用。该基于氨基酸的可聚合化合物的化学式为I：其中R，R1和R2如本文所述。
• Zwitterionic Guanidine-Based Oligomers Mimicking Cell-Penetrating Peptides as a Nontoxic Alternative to Cationic Polymers to Enhance the Cellular Uptake of Micelles
  作者：Yoseop Kim、Sandra Binauld、Martina H. Stenzel

  DOI：10.1021/bm301351e

  日期：2012.10.8

  The aim of this work is to generate polymer micelles decorated with a synthetic version of cell-penetrating peptides, which are often rich in arginine with its positively charged guanidine group. A methacrylate-based monomer with guanidinium as functional groups was prepared using arginine (M-Arg) as a building block, resulting in a zwitterionic monomer. RAFT (reversible addition-fragmentation chain transfer) polymerization was employed to generate triblock copolymers with poly(methyl methacrylate)-block-poly(polyethylene glycol methyl ether methacrylate) as the first two blocks, which were subsequently chain extended with the guanidine-based monomer to generate micelles with guanidinium functional groups on the surface. To simulate the actual oligoarginine peptide, which only carries cationic charges, the carboxylate group of P(M-Arg) was methylated to convert the zwitterionic polymer into a cationic polymer P(Me-M-Arg). For comparison, micelles based on triblock copolymers with a third block with permanently cationic charges, poly(2-methacryolyloxy ethyl) trimethyl ammonium chloride (PTMA), was prepared. The hydrodynamic diameters of the micelles were approximately 30-40 nm based on DLS and TEM. A direct correlation between surface charge (zeta potential zeta) and cytotoxicity was observed. The micelles based on the zwitterionic P(M-Arg) were nontoxic (zeta = -10 mV at pH = 7), while the methylated version P(Me-M-Arg) with a high cationic charge (zeta = +35 mV at pH = 7) were observed to be toxic. The cellular uptake of the block copolymers by OVCAR-3 ovarian cancer cell lines was found to be relatively fast (about 35% in 3 min) reaching an equilibrium after approximately 30 min. Both micelles, with either P(M-Arg) or P(Me-M-Arg) on the surface, showed an enhanced uptake compared to micelles with P(PEGMEMA) as shell only. In fact, the percentage of uptake was similar, with the difference that cells incubated with micelles with P(M-Arg) (zwitterionic) stayed alive, while P(Me-M-Arg) (cationic) led to significant cell death.
• Solubilization of organic compounds by arginine-derived polymers
  作者：Xuchen Huang、Yanbin Huang

  DOI：10.1016/j.cclet.2015.04.009

  日期：2015.6

  Poor aqueous solubility of drugs is one of the major challenges in the pharmaceutical science. In this study, a guanidinium-containing polymer based on arginine was designed and synthesized, and was evaluated as a solubility enhancing additive for three model organic compounds (coumarin, pyrene and doxorubicin). At a guanidinium group concentration of 100 mmol/L, the polymer could significantly increase the solubility of pyrene and doxorubicin by 6- and 11-fold respectively, much more effective than arginine (2- and 3-fold, respectively). In contrast, its effect on the solubility of coumarin was less effective than arginine. The solubilizing effect may be explained by the enhanced interaction between the guanidinium group in the polymer and the aromatic compounds. (C) 2015 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.
• CORONA-LIKE (GUANIDYL)-OLIGOSACCHARIDIC DERIVATIVES AS CELL-PENETRATING ENHANCERS FOR INTRACELLULAR DELIVERY OF COLLOIDAL THERAPEUTIC SYSTEMS
  申请人：Universita' Degli Studi Di Padova

  公开号：EP2665736B1

  公开（公告）日：2015-09-16