N-α-benzoyl-DL-arginine-p-nitroanilide | 911-76-2

• 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: N-α-benzoyl-DL-arginine-p-nitroanilide
• 英文别名: N_α-benzoyl-DL-arginine-p-nitroanilide；α-N-Benzoyl-D,L-arginine-p-nitroanilide；Nα-benzoyl-DL-arginine-p-nitroanilidine；α-N-benzoyl-DL-arginine p-nitroanilide；α-N-benzoyl-DL-arginine-p-nitroanilide；N-α-benzoyl-DL-arginine 4-nitroanilide
• CAS: 911-76-2；6208-93-1；7723-66-2；26056-64-4
• 化学式: C₁₉H₂₂N₆O₄
• 分子量: 398.421
• InChiKey: RKDYKIHMFYAPMZ-UHFFFAOYSA-N

物化性质

• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  168
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-α-benzoyl-DL-arginine-p-nitroanilide 在 trypsin 作用下， 以 aq. buffer 为溶剂， 反应 0.13h， 生成 4-硝基苯胺
  参考文献：
  名称：

  肿瘤微环境特异性激活蛋白活性的模块化和门控传递平台。

  摘要：

  蛋白质疗法激发了人们在各个领域的广泛研究兴趣。仍然迫切需要避免治疗性蛋白质的过早或意外活化，以实现对治疗的高度特异性。在此，我们报道了一种基于分子胶粘附的蛋白质生物矿化的模块化AND门控递送平台，用于肿瘤微环境特异性激活治疗性蛋白质活性。AND门将肿瘤组织的特定微环境（酸性pH和ATP的一定浓度）整合为输入，并且仅在两个输入均激活时才激活蛋白质的治疗活性。更重要的是，无论在酸性pH还是在ATP存在下，治疗蛋白的活性都不会被激活，这可以大大避免对正常组织的有害影响。除了，

  DOI：

  10.1002/chem.202000219

文献信息

• Preparation and characterization of biodegradable or enteric-coated microspheres containing the protease inhibitor camostat
  作者：Takahiro Uchida、Noriko Yasuda、Kenji Matsuyama

  DOI：10.1211/0022357011775280

  日期：2010.2.18

  We have produced biodegradable or enteric-coated microspheres containing camostat mesylate, a protease inhibitor, using a water-oil-water emulsion solvent evaporation method. The characteristics of the microspheres were determined. When polylactic acid, a biodegradable polymer, was used as a wall material, the optimized microsphere obtained showed a loading efficiency of almost 95% and had a mean diameter of 30 pim. This microsphere showed a sustained-release profile, with nearly 25% of drug being released at seven days in a dissolution test. When hypromellose acetate succinate (AS-HG type, with a high content of succinyl group) was used as an enteric wall material, optimized microspheres showed a loading efficiency of almost 80%. In this case, pH 3.0 citrate buffer was used as an internal aqueous phase, and citrate buffer containing 0.5 % polyvinylalcohol was used as the external aqueous phase. These microspheres showed a rapid release profile in pH 6.8 buffer, whereas the release was extremely slow in pH 1.2 buffer. Hypromellose acetate succinate microspheres were also prepared containing 10% (w/w) N-benzoyl-dl-arg-4-nitroanilide as a model substrate for trypsin, with or without 5% (w/w) camostat. These microspheres were incubated in pH 6 or 7 buffer containing trypsin at 37°C. When camostat was included in the microspheres, the substrate was protected from attack by trypsin, while in the absence of camostat, the released substrate was immediately attacked by trypsin to produce the degradation product N-benzoyl-dl-arginine.

  摘要：我们使用水油水乳化溶剂蒸发法制备了含有蛋白酶抑制剂卡莫司他的生物可降解或肠溶性微球。确定了微球的特性。当使用生物可降解聚乳酸作为壁材料时，优化的微球的负荷效率几乎达到了95％，平均直径为30微米。这种微球表现出缓释特性，在溶解试验中，在七天内释放了近25％的药物。当使用富含琥珀酸基的羟甲基纤维素醋酸酯（AS-HG型）作为肠溶性壁材料时，优化的微球的负荷效率几乎达到了80％。在这种情况下，pH 3.0的柠檬酸盐缓冲液被用作内部水相，含0.5％聚乙烯醇的柠檬酸盐缓冲液被用作外部水相。这些微球在pH 6.8缓冲液中表现出快速释放特性，而在pH 1.2缓冲液中释放极慢。还制备了含有10％（w / w）N-苯酰-dl-精氨酰-4-硝基苯胺作为胰蛋白酶模型底物的羟甲基纤维素醋酸酯微球，其中包含或不包含5％（w / w）卡莫司他。这些微球在含有胰蛋白酶的pH 6或7缓冲液中孵育37°C。当微球中包含卡莫司他时，底物被保护免受胰蛋白酶的攻击，而在没有卡莫司他的情况下，释放的底物立即被胰蛋白酶攻击，产生降解产物N-苯酰-dl-精氨酸。
• Method for isolating alpha-1-antitrypsin
  申请人：Medical Research Institute of San Francisco

  公开号：EP0067293A2

  公开（公告）日：1982-12-22

  Alpha-1-antitrypsin is isolated from solutions of protein containing alpha-1-antitrypsin, such as human plasma. Isolation is accomplished by breaking sufficient disulfide bonds in the proteins to destabilize them. Reducing agents such as dithiothreitol are used to break the disulfide bonds. The destabilized proteins may be precipitated by salting out. Alpha-l-antitrypsin is not stabilized by disulfide bonds, is therefore not destabilized by the treatment, and can be recovered from the supernatant by chromatographic separation. Other suitable proteins such as antichymotrypsin may be similarly isolated.

  α-1-抗胰蛋白酶是从含有α-1-抗胰蛋白酶的蛋白质溶液（如人体血浆）中分离出来的。分离的方法是破坏蛋白质中足够的二硫键，使其失去稳定性。二硫苏糖醇等还原剂可用于断开二硫键。脱稳的蛋白质可通过盐析沉淀出来。α-l-抗胰蛋白酶没有被二硫键稳定，因此不会因处理而失稳，可通过色谱分离从上清液中回收。其他合适的蛋白质，如抗糜蛋白酶，也可同样分离出来。
• Benzisothiazolinone-1-dioxide derivatives as elastase inhibitors
  申请人：UNILEVER PLC

  公开号：EP0446047A1

  公开（公告）日：1991-09-11

  The invention relates to pharmaceutical and cosmetic compositions comprising at least one benzisothiazolinone-1-dioxide derivative with the formula: where R¹ can be hydrogen, and R² can be certain generally hydrophobic C₈-C₂₀ aliphatic groups or the group: where R⁵ is aliphatic or else R² is a saturated or unsaturated C₂-C₆ group ending in an aromatic nucleus. These compositions can be used to inhibit elastases such as human leucocytic elastase. They may be applied topically as a cosmetic. Many of the benzisothiazolinone-1-dioxide derivative specified as active ingredient in such compositions are novel compounds.

  本发明涉及包含至少一种苯并异噻唑啉酮-1-二氧化物衍生物的药物和化妆品组合物，其化学式为 其中 R¹ 可以是氢，R² 可以是某些一般疏水的 C₈-C₂₀ 脂肪族基团或基团： 其中 R⁵ 是脂肪族，否则 R² 是以芳香核结尾的饱和或不饱和 C₂-C₆ 基团。 这些成分可用于抑制弹性蛋白酶，如人白细胞弹性蛋白酶。它们可作为化妆品局部使用。 许多被指定为此类组合物活性成分的苯并异噻唑啉酮-1-二氧化物衍生物都是新型化合物。
• Processes for the preparation of amylase inhibitor
  申请人：NISSHIN FLOUR MILLING CO., LTD.

  公开号：EP0567088A2

  公开（公告）日：1993-10-27

  A process for the preparation of an amylase inhibitor is disclosed which comprises the steps of: (a) extracting wheat, wheat flour or wheat gluten with water, a dilute acid, a dilute alkali or an aqueous alcohol to produce a solution containing the amylase inhibitor; (b) adding a polysaccharide to said solution to form an insoluble complex of the amylase inhibitor with the polysaccharide and separating the insoluble complex from the solution; (c) dissolving or dispersing said complex in a solution, then separating the polysaccharide from the solution to collect a solution containing the amylase inhibitor; and (d) treating the collected solution with a cation exchanger to recover the amylase inhibitor from fractions that have not been adsorbed on the cation exchanger. The amylase inhibitors produced by the above process possess a high amylase inhibitory activity but substantially no trypsin inhibitory activity, and are useful in the prophylaxis and treatment of diseases such as hyperglycemia, diabetes, hyperlipemia, arteriosclerosis and obesity.

  本发明公开了一种制备淀粉酶抑制剂的工艺，该工艺包括以下步骤 (a) 用水、稀酸、稀碱或含水酒精提取小麦、小麦粉或小麦麸质，生成含有淀粉酶抑制剂的溶液； (b) 向所述溶液中加入多糖，使淀粉酶抑制剂与多糖形成不溶性复合物，并将不溶性复合物从溶液中分离出来； (c) 将所述复合物溶解或分散在溶液中，然后将多糖从溶液中分离出来，收集含有淀粉酶抑制剂的溶液；以及 (d) 用阳离子交换剂处理收集到的溶液，从阳离子交换剂上未吸附的馏分中回收淀粉酶抑制剂。 上述工艺生产的淀粉酶抑制剂具有很高的淀粉酶抑制活性，但基本上没有胰蛋白酶抑制活性，可用于预防和治疗高血糖、糖尿病、高脂血症、动脉硬化和肥胖症等疾病。
• METHOD FOR SEARCHING FOR PEPTIDES AND PROCESS FOR PRODUCING COMPOUNDS
  申请人：YAMANOUCHI PHARMACEUTICAL CO., LTD.

  公开号：EP0916677A1

  公开（公告）日：1999-05-19

  Peptides having a higher physiological activity are screened by the steps of (a) synthesizing an optional number of peptides having different arbitrary amino acid sequences; (b) assaying the peptides synthesized in step (a) for their physiological activities to select an optional number of peptides having higher physiological activities; (c) synthesizing peptides having amino acid sequences obtained by genetic algorithm processing of the amino acid sequences of the peptides selected in step (b); and, (d) repeating step (b) and step (c), an optional number of times, for the peptides obtained in step (c). In genetic algorithms, each amino acid is represented by one notation and amino acid sequence of a peptide by the representation is used as a genome.

  通过以下步骤筛选具有较高生理活性的多肽：(a) 合成具有不同任意氨基酸序列的可选数量的多肽；(b) 检测步骤(a)中合成的多肽的生理活性，以选择具有较高生理活性的可选数量的多肽；(c) 合成具有通过遗传算法处理步骤(b)中选出的多肽的氨基酸序列而获得的氨基酸序列的多肽；以及 (d) 对于步骤(c)中获得的多肽，重复步骤(b)和步骤(c)，次数任选。在遗传算法中，每个氨基酸用一个符号表示，用该符号表示的肽的氨基酸序列被用作基因组。