Ac-Ala-Ala-Pro-OH | 63769-88-0

• 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: Ac-Ala-Ala-Pro-OH
• 英文别名: Acetylalanylalanylproline；(2S)-1-[(2S)-2-[[(2S)-2-acetamidopropanoyl]amino]propanoyl]pyrrolidine-2-carboxylic acid
• CAS: 63769-88-0
• 化学式: C₁₃H₂₁N₃O₅
• 分子量: 299.327
• InChiKey: STHAWVJUFITXLV-NRPADANISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.91
• 重原子数：
  21.0
• 可旋转键数：
  5.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  115.81
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  Ac-Ala-Ala-Pro-OH 在 N-甲基吗啉 作用下， 以 氯仿 、 乙腈 为溶剂， 反应 4.0h， 生成 N-acetyl-L-alanyl-L-alanyl-N-(3,3,3-trifluoro-2-hydroxy-1-methylpropyl)-L-prolinamide
  参考文献：
  名称：

  Synthesis of peptidyl fluoromethyl ketones and peptidyl .alpha.-keto esters as inhibitors of porcine pancreatic elastase, human neutrophil elastase, and rat and human neutrophil cathepsin G

  摘要：

  Comparison of MeO-Suc-Val-Pro-Phe-CO2Me (29) and MeO-Suc-Ala-Ala-Pro-Phe- CO2Me (25) with their corresponding trifluoromethyl ketones 9a and 9b, respectively, in rat and human neutrophil cathepsin G assays showed the alpha-keto esters to be more potent inhibitors. Likewise, Ac-Pro-Ala-Pro-Ala-CO2Me (21) was more potent than its corresponding trifluoromethyl ketone (9c) in both porcine pancreatic elastase and human neutrophil elastase assays. Within a set of Ala-Ala-Pro-Val-CF3 elastase inhibitors, the carbobenzyloxy (Cbz) N-protecting group conferred greater potency as a P5 site recognition unit for elastase than did dansyl, methoxysuccinyl, or tert-butyloxycarbonyl. Initial inhibition of elastase was greater when trifluoromethyl ketone 9f was added from a stock solution of dimethyl sulfoxide than when it had been buffer-equilibrated prior to assay, which suggests that the nonhydrated ketone is the more effective form of the inhibitor. The most potent elastase inhibitor we report is Na-(Ad-SO2)-N epsilon-(MeO-Suc)Lys-Pro-Val-CF3 (16) which has a Ki of 0.58 nM.

  DOI：

  10.1021/jm00163a063

文献信息

• Peptide carbazates
  申请人：Merck & Co., Inc.

  公开号：US04029772A1

  公开（公告）日：1977-06-14

  Certain novel peptide carbazates, their preparation, pharmaceutical compositions and novel methods of treating pancreatitis.

  某些新型肽氨基甲酰肼及其制备、制药组合物和治疗胰腺炎的新方法。
• Peptide carbazates and pharmaceutical composition
  申请人：Merck & Co., Inc.

  公开号：US04064236A1

  公开（公告）日：1977-12-20

  Certain novel peptide carbazates, their preparation, pharmaceutical compositions and novel methods of treating pancreatitis.

  某些新型肽类卡巴曲酰胺、它们的制备、制药组合物和治疗胰腺炎的新方法。
• A Tandem‐Locked Fluorescent NETosis Reporter for the Prognosis Assessment of Cancer Immunotherapy
  作者：Penghui Cheng、Shasha He、Chi Zhang、Jing Liu、Kanyi Pu

  DOI：10.1002/anie.202301625

  日期：2023.6.26

  NETosis, the peculiar type of neutrophil death, plays important roles in pro‐tumorigenic functions and inhibits cancer immunotherapy. Non‐invasive real‐time imaging is thus imperative for prognosis of cancer immunotherapy yet remains challenging. Herein, we report a Tandem‐locked NETosis Reporter 1 (TNR₁) that activates fluorescence signals only in the presence of both neutrophil elastase (NE) and cathepsin G (CTSG) for the specific imaging of NETosis. In the aspect of molecular design, the sequence of biomarker‐specific tandem peptide blocks can largely affect the detection specificity towards NETosis. In live cell imaging, the tandem‐locked design allows TNR₁ to differentiate NETosis from neutrophil activation, while single‐locked reporters fail to do so. The near‐infrared signals from activated TNR₁ in tumor from living mice were consistent with the intratumoral NETosis levels from histological results. Moreover, the near‐infrared signals from activated TNR₁ negatively correlated with tumor inhibition effect after immunotherapy, thereby providing prognosis for cancer immunotherapy. Thus, our study not only demonstrates the first sensitive optical reporter for noninvasive monitoring of NETosis levels and evaluation of cancer immunotherapeutic efficacy in tumor‐bearing living mice, but also proposes a generic approach for tandem‐locked probe design.

  摘要嗜中性粒细胞死亡（NETosis）是一种特殊的嗜中性粒细胞死亡类型，在促肿瘤生成功能和抑制癌症免疫治疗方面发挥着重要作用。因此，非侵入性实时成像对于癌症免疫治疗的预后至关重要，但仍具有挑战性。在此，我们报告了一种串联锁定的 NETosis Reporter 1（TNR1），它只有在中性粒细胞弹性蛋白酶（NE）和凝血酶 G（CTSG）同时存在的情况下才能激活荧光信号，用于 NETosis 的特异性成像。在分子设计方面，生物标记物特异性串联肽段的序列会在很大程度上影响对 NETosis 的检测特异性。在活细胞成像中，串联锁定设计允许 TNR1 将 NETosis 与中性粒细胞活化区分开来，而单个锁定的报告物则无法做到这一点。活体小鼠肿瘤中活化的 TNR1 发出的近红外信号与组织学结果显示的瘤内 NETosis 水平一致。此外，活化 TNR1 的近红外信号与免疫治疗后的肿瘤抑制效果呈负相关，从而为癌症免疫治疗提供了预后依据。因此，我们的研究不仅首次展示了用于无创监测肿瘤活体小鼠NETosis水平和评估癌症免疫治疗效果的灵敏光学报告器，还提出了串联锁定探针设计的通用方法。
• US4029772A
  申请人：——

  公开号：US4029772A

  公开（公告）日：1977-06-14
• US4064236A
  申请人：——

  公开号：US4064236A

  公开（公告）日：1977-12-20