Boc-Pro-Ala-Lys(Z)-OBzl | 202410-99-9

• 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: Boc-Pro-Ala-Lys(Z)-OBzl
• 英文别名: tert-butyl (2S)-2-[[(2S)-1-oxo-1-[[(2S)-1-oxo-1-phenylmethoxy-6-(phenylmethoxycarbonylamino)hexan-2-yl]amino]propan-2-yl]carbamoyl]pyrrolidine-1-carboxylate
• CAS: 202410-99-9
• 化学式: C₃₄H₄₆N₄O₈
• 分子量: 638.761
• InChiKey: KGMKKJJYQLLBPQ-WIRXVTQYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  46
• 可旋转键数：
  18
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  152
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Boc-Pro-Ala-Lys(Z)-OBzl 在 盐酸 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 153.0h， 生成 N-[1-(1',3'-dioxyl-4',4',5',5'-tetramethyldihydroimidazol-2-yl)phenyl-4-yl]oxyacetyl-Ala-Arg(Tos)-Pro-Ala-Lys(Z)-OBzl
  参考文献：
  名称：

  Synthesis and Biological Activity of Nitronyl Nitroxide Containing Peptides

  摘要：

  [1-(1 ',3 '-Dioxyl-4 ',4 ',5 ',5 '-tetramethyldihydroimidazol-2-yl)-phenyl-4-yl]oxyacetic acid (4), a nitronyl nitroxide, and its peptide derivatives, N-[1-(1 ',3 '-dioxyl-4 ',4 ',5 ',5 '-tetramethyldihydroimidazol-2-yl)-phenyl-4-yl]oxyacetyl-ARPAK (9a), -GRPAK (9b), and -QRPAK (9c), were synthesized and characterized. Judging from the results of electron spin resonance analysis, the newly synthesized nitronyl nitroxide containing peptides, 9a, 9b, and 9c, demonstrated the characteristics of free radicals. The free radical scavenging activities of 9a, 9b, and 9c were assessed using in vitro free radical scavenging tests. The thrombolysis effect of 9a, 9b, and 9c was evaluated using an euglobulin clot lysis test, a fibrinolytic lysis test, and in vivo thrombolysis tests. Results indicated that these nitronyl nitroxide containing peptides possessed both free radical scavenging activity and thrombolytic activity.

  DOI：

  10.1021/jm050050k
• 作为产物：
  描述：

  N-Boc-N'-Cbz-L-赖氨酸 在 盐酸 、 1-羟基苯并三唑 、 caesium carbonate 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 乙醇 、 乙酸乙酯 为溶剂， 反应 119.0h， 生成 Boc-Pro-Ala-Lys(Z)-OBzl
  参考文献：
  名称：

  Synthesis and Biological Activity of Nitronyl Nitroxide Containing Peptides

  摘要：

  [1-(1 ',3 '-Dioxyl-4 ',4 ',5 ',5 '-tetramethyldihydroimidazol-2-yl)-phenyl-4-yl]oxyacetic acid (4), a nitronyl nitroxide, and its peptide derivatives, N-[1-(1 ',3 '-dioxyl-4 ',4 ',5 ',5 '-tetramethyldihydroimidazol-2-yl)-phenyl-4-yl]oxyacetyl-ARPAK (9a), -GRPAK (9b), and -QRPAK (9c), were synthesized and characterized. Judging from the results of electron spin resonance analysis, the newly synthesized nitronyl nitroxide containing peptides, 9a, 9b, and 9c, demonstrated the characteristics of free radicals. The free radical scavenging activities of 9a, 9b, and 9c were assessed using in vitro free radical scavenging tests. The thrombolysis effect of 9a, 9b, and 9c was evaluated using an euglobulin clot lysis test, a fibrinolytic lysis test, and in vivo thrombolysis tests. Results indicated that these nitronyl nitroxide containing peptides possessed both free radical scavenging activity and thrombolytic activity.

  DOI：

  10.1021/jm050050k

文献信息

• NOVEL COMPOUND WITH EFFECTS OF THROMBOLYSIS, FREE RADICAL SCAVENGING AND THROMBUS-TARGETING AS WELL AS PREPARATION METHOD AND USE THEREOF
  申请人：Shanghai Lumosa Therapeutics, Co., Ltd.

  公开号：US20150290339A1

  公开（公告）日：2015-10-15

  The present invention discloses a novel compound with effects of thrombolysis, free radical scavenging and thrombus-targeting, as well as a preparation method and use thereof. The compound is a ternary conjugate formed by conjugating a thrombolytic peptide, a free radical scavenger and a thrombus-targeting/antithrombotic peptide together via a linking arm. The present invention also discloses a pharmaceutical composition containing the compounds, wherein the compounds form a nanospherical structure.

  本发明公开了一种具有溶栓、清除自由基和靶向血栓作用的新型化合物，以及其制备方法和用途。该化合物是通过连接臂将溶栓肽、自由基清除剂和靶向/抗血栓肽结合在一起形成的三元共轭物。本发明还公开了含有这些化合物的药物组合物，其中这些化合物形成纳米球状结构。
• DHDMIQK(KAP): a novel nano-delivery system of dihydroxyl-tetrahydro-isoquinoline-3-carboxylic acid and KPAK towards the thrombus
  作者：Qiqi Feng、Ming Zhao、Taiping Gan、Haimei Zhu、Yaonan Wang、Shurui Zhao、Yuji Wang、Jianhui Wu、Shiqi Peng

  DOI：10.1039/c6tb00874g

  日期：——

  N-[(S)-6,7-Dihydroxy-1,1-dimethyl-1,2,3,4-tetra-hydroisoquinoline-3-carbonyl]-Lys(Pro-Ala-Lys) was presented as a novel nano-delivery of (S)-6,7-dihydroxy-1,1-dimethyl-1,2,3,4-tetra-hydroisoquinoline-3-carboxylic acid and Lys-Pro-Ala-Lys towards the thrombus for the first time.

  首次提出一种新型纳米递送体，即N-[(S)-6,7-二羟基-1,1-二甲基-1,2,3,4-四氢异喹啉-3-羧酰基]-Lys(Pro-Ala-Lys)，用于传递(S)-6,7-二羟基-1,1-二甲基-1,2,3,4-四氢异喹啉-3-羧酸和Lys-Pro-Ala-Lys至血栓。
• Zhao, Ming; Peng, Shiqi, Advanced Synthesis and Catalysis, 1999, vol. 341, # 7, p. 668 - 676
  作者：Zhao, Ming、Peng, Shiqi

  DOI：——

  日期：——
• A new class of β-carboline alkaloid-peptide conjugates with therapeutic efficacy in acute limb ischemia/reperfusion injury
  作者：Wei Bi、Yue Bi、Ping Xue、Yanrong Zhang、Xiang Gao、Zhibo Wang、Meng Li、Michèle Baudy-Floc’h、Nathaniel Ngerebara、K. Michael Gibson、Lanrong Bi

  DOI：10.1016/j.ejmech.2011.01.021

  日期：2011.5

  We describe a novel class of beta-carboline alkaloid-peptide conjugates that possess both free radical scavenging and thrombolytic activity. These conjugates demonstrate therapeutic efficacy in a rat arterial thrombosis assay, as well as free radical scavenging capacity as evaluated in a PC12 cell survival assay. Our results indicate that beta-carboline alkaloid-peptide conjugate 26a exerts a significant protective effect against local and remote organ injury induced by limb I/R injury in the rat. Published by Elsevier Masson SAS.
• The composition and sequence specificity of Pro-Ala-Lys-OH for the thrombolytic activities of P6A and related oligopeptides
  作者：Ming Zhao、Chao Wang、Jiangyuan Liu、Kexiang Zhou、Shiqi Peng

  DOI：10.1016/j.bmc.2004.02.011

  日期：2004.5

  The in vitro and in vivo thrombolytic activities of Ala-Arg-Pro-Ala-Lys-OH, its analogs and the related peptides were assayed. The results indicate that when (5)Lys of Ala-Arg-Pro-Ala-Lys-OH is changed into (5)Arg, and (5)Lys of Pro-Ala-Lys-OH is changed into (3)Arg the thrombolytic activities are collapsed; when Pro-Ala-Lys-OH is changed into Ala-Pro-Lys-OH, and Ala-Arg-Pro-Ala-Lys-OH is changed into Ala-Arg-Ala-Pro-Lys-OH the thrombolytic activities are also collapsed; when (5)nLys of Ala-Arg-Pro-Ala-Lys-OH is changed into (5)nLeu the thrombolytic activities are again collapsed. All of the results indicate that for the thrombolytic activities of Ala-Arg-Pro-Ala-Lys-OH and the related peptides Pro-Ala-Lys-OH exhibits either amino acid composition specificity or sequence specificity. The composition and sequence specificity of Pro-Ala-Lys-OH reflects its rule as the pharmacophore of P6A and the related peptides. (C) 2004 Elsevier Ltd. All rights reserved.