H-甘氨酸-脯氨酸-精氨酸-脯氨酸-OH乙酸盐 | 67869-62-9

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 精氨酸类衍生物
• 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
• 中文名称: H-甘氨酸-脯氨酸-精氨酸-脯氨酸-OH乙酸盐
• 英文名称: Gly-Pro-Arg-Pro
• 英文别名: glycyl-L-prolyl-L-arginyl-L-prolin；Glycyl-prolyl-arginyl-proline；(2S)-1-[(2S)-2-[[(2S)-1-(2-aminoacetyl)pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carboxylic acid
• CAS: 67869-62-9
• 化学式: C₁₈H₃₁N₇O₅
• 分子量: 425.488
• InChiKey: WXPZDDCNKXMOMC-AVGNSLFASA-N

物化性质

• 熔点：
  123-125 °C
• 密度：
  1.55±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO：20.83（最大浓度 mg/mL）；42.9（最大浓度 mM）

计算性质

• 辛醇/水分配系数(LogP)：
  -4.7
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  197
• 氢给体数：
  5
• 氢受体数：
  7

安全信息

• WGK Germany：
  3

制备方法与用途

生物活性方面，GPRP 是一种纤维蛋白聚合抑制剂，能够阻止纤维蛋白原与血小板膜糖蛋白 IIb/IIIa 复合物（即糖蛋白 IIb/IIIa 受体）的结合。

反应信息

• 作为产物：
  描述：

  叔丁氧羰基-脯氨酰-琥珀酰亚胺 在 盐酸 、 sodium hydroxide 、 TEA 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 乙酸乙酯 为溶剂， 生成 H-甘氨酸-脯氨酸-精氨酸-脯氨酸-OH乙酸盐
  参考文献：
  名称：

  Synthesis of modified fragments of fibrinogen and their effect on the activity of proteolytic enzymes

  摘要：

  New analogues of the Gly-Pro-Arg and Arg-Gly-Asp fragments of fibrinogen were synthesized: Gly-Pro-Arg-Pro (1), Gly-Pro-Arg-Pro-Met-We (11), Gly-Pro-Arg-Pro-Phe (111), Gly-Pro-Arg-Pro-Asp (IV), Gly-Pro-Arg-Pro-Glu (V), and Arg-Asn-Trp-Asp (VI). Their effect on the activity of proteases of various types was studied with the method of lysis of fibrin plates. All the peptides were found to inhibit plasmin activity (by 60-85%) and the gamma-subunit of nerve growth factor (by 55-93%). Tetrapeptide (VI) proved to be an effective inhibitor of tissue activator of plasminogen and the 7-subunit of nerve growth factor (by 96 and 93%, respectively). The peptides exerted practically no effect on the activity of urokinase and moderately inhibited the activity of streptokinase [(III), IV), and (VI)], papain [(I), (II), IV), and (VI)], subtilisin [(V) and (VI)], (x-chymotrypsin [(III), (V), and VI)], and Bacillus subtilis metalloprotease (VI). They inhibit trypsin [except for (1) and (111)] when applied on fibrin plates at a concentration of I X 10(-2) M, while, at the concentration of I X 10(-3) M, (1) and (11) induced an increase in proteolytic activity by 35 and 47%, respectively.

  DOI：

  10.1134/s106816200602004x

文献信息

• Sustainable Peptide Synthesis Enabled by a Transient Protecting Group
  作者：Sascha Knauer、Niklas Koch、Christina Uth、Reinhard Meusinger、Olga Avrutina、Harald Kolmar

  DOI：10.1002/anie.202003676

  日期：2020.7.27

  (Smoc) protecting group. This approach enables peptide assembly under aqueous conditions, real‐time monitoring of building block coupling, and efficient postsynthetic purification. The procedure for the synthesis of all natural and several non‐natural Smoc‐protected amino acids is described, as well as the assembly of 22 peptide sequences and the fundamental issues of SPPS, including the protecting group

  对合成肽的兴趣日益增长，促使人们开发出可持续的生产方法。当前，从受保护的结构单元组装肽需要大量有毒溶剂，并且转换为水作为反应介质仍然是肽化学中的主要障碍。我们报告了一种基于水相容性2,7-二硫代-9-芴基甲氧基羰基（Smoc）保护基的固相肽水合成策略。这种方法可在水性条件下进行肽组装，实时监测构件偶联以及有效的合成后纯化。描述了合成所有天然和几种非天然Smoc保护的氨基酸的程序，以及22种肽序列的组装和SPPS的基本问题，
• Amino Acids and Peptides. XVI. Synthesis of N-Terminal Tetrapeptide Analogy of Fibrin .ALPHA.-Chain and Their Inhibitory Effects on Fibrinogen/Thrombin Clotting.
  作者：Koichi KAWASAKI、Katsuhiko HIRASE、Masanori MIYANO、Toshiki TSUJI、Masanori IWAMOTO

  DOI：10.1248/cpb.40.3253

  日期：——

  N-Terminal tetrapeptide analogs of fibrin α-chain were synthesized by the solution method using a new active ester, the ester of the oxime of p-nitroacetophenone, and by the solid-phase method. Their inhibitory effects on fibrinogen/thrombin clotting were examined. Of the synthetic peptides, amide analogs of Gly-Pro-Arg-Pro exhibited a more potent inhibitory effect.

  采用溶液法和固相法合成了纤维蛋白α链的N端四肽类似物，使用了一种新的活性酯，即对硝基乙酰苯酮的腙酯。考察了它们对纤维蛋白原/凝血酶凝固的抑制作用。在合成的肽中，甘氨酸-脯氨酸-精氨酸-脯氨酸的酰胺类似物表现出更强的抑制效果。
• [EN] ANTITHROMBOTIC AZACYCLOALKYLALKANOYL PEPTIDES AND PSEUDOPEPTIDES<br/>[FR] PEPTIDES ET PSEUDOPEPTIDES A GROUPE AZACYCLOALKYLALCANOYLE AYANT DES PROPRIETES ANTITHROMBOTIQUES
  申请人：RHONE-POULENC RORER PHARMACEUTICALS INC.

  公开号：WO1995010295A1

  公开（公告）日：1995-04-20

  (EN) The present invention relates to azacycloalkylalkanoyl peptides and pseudopeptides which inhibit platelet aggregation and thrombus formation thereby being useful in the prevention and treatment of thrombosis associated with disease states such as myocardial infarction, stroke, peripheral arterial disease, and disseminated intravascular coagulation, to methods for the prevention or treatment of thrombosis in a mammal in need of such therapy comprising the administration of a therapeutically effective amount of such compounds, and to pharmaceutical compositions comprising such compounds.(FR) La présente invention concerne des peptides ou pseudopeptides à groupe azacycloalkylalcanoyle qui inhibent l'agrégation plaquettaire et la formation de thrombus, ce qui les rend utiles dans la prévention et le traitement de thromboses que l'on rencontre dans des états pathologiques tels que l'infarctus du myocarde, les accidents cérébrovasculaires, les maladies vasculaires périphériques, et la coagulation intravasculaire disséminée. L'invention concerne également des méthodes de prévention ou de traitement de thromboses chez des mammifères nécessitant une telle thérapie, consistant à d'administrer une dose appropriée de tels composés, ainsi que des compositions pharmaceutiques comprenant de tels composés.

  本发明涉及抑制血小板聚集和血栓形成的氮杂环烷基烷酰肽和假肽，因此可用于预防和治疗与疾病状态相关的血栓形成，如心肌梗死、中风、外周动脉疾病和弥漫性血管内凝血，以及用于治疗需要此类治疗的哺乳动物的预防或治疗血栓形成的方法，包括给予这些化合物的治疗有效量，以及包含这些化合物的制药组合物。
• Antithrombotic azacycloalkylalkanoyl peptides and pseudopeptides
  申请人：——

  公开号：US20020002268A1

  公开（公告）日：2002-01-03

  The present invention relates to azacycloalkylalkanoyl peptides and pseudopeptides which inhibit platelet aggregation and thrombus formation thereby being useful in the prevention and treatment of thrombosis associated with disease states such as myocardial infarction, stroke, peripheral arterial disease, and disseminated intravascular coagulation, to methods for the prevention or treatment of thrombosis in a mammal in need of such therapy comprising the administration of a therapeutically effective amount of such compounds, and to pharmaceutical compositions comprising such compounds.

  本发明涉及抑制血小板聚集和血栓形成的氮杂环烷基烷酰肽和伪肽，因此在预防和治疗与疾病状态相关的血栓形成，如心肌梗死、中风、外周动脉疾病和弥漫性血管内凝血等方面具有用处，以及用于预防或治疗哺乳动物中需要此类治疗的方法，包括给予这些化合物的治疗有效量，以及包含这些化合物的制药组合物。
• Highly sensitive, accurate and precise automated method and device for identifying and quantifying platelets and for determining platelet activation state using whole blood samples
  申请人：Bayer Corporation

  公开号：EP0784201A2

  公开（公告）日：1997-07-16

  The present invention provides a highly sensitive and accurate method and system for the discrimination and quantification of platelets in a whole blood sample using automated hematology instruments. The method and system of the invention provide the accurate measurements of platelet dry mass and platelet component concentration in both normal blood samples and in abnormal blood samples, such as those from thrombocytopenic patients. The determination of platelet dry mass and platelet component concentration can serve to assess the activation state of platelets since activated platelets possess measurably lower component concentrations and refractive indices than do unactivated platelets. The method and system of the invention also allows the clinician or skilled practitioner to determine the age of a blood sample on the basis of the measured parameter of platelet component concentration.

  本发明提供了一种高灵敏度、高准确度的方法和系统，可利用自动血液学仪器对全血样本中的血小板进行鉴别和定量。本发明的方法和系统可准确测量正常血样和异常血样（如血小板减少症患者的血样）中的血小板干质量和血小板成分浓度。血小板干质量和血小板成分浓度的测定可用于评估血小板的活化状态，因为活化血小板的成分浓度和折射率明显低于未活化血小板。本发明的方法和系统还允许临床医生或熟练从业人员根据血小板成分浓度的测量参数确定血液样本的年龄。