Ac-Asp(OBu-t)-Glu(OBu-t)-Val-Asp(OBu-t)

• 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-Asp(OBu-t)-Glu(OBu-t)-Val-Asp(OBu-t)
• 英文别名: Ac-D(O-tBU)E(O-tBU)VD(O-tBU)-COOH；Ac-Asp(O^tBu)-Glu(O^tBu)-Val-Asp(O^tBu)-COOH；Ac-D(OtBu)E(OtBu)VD(OtBu)-OH；Ac-Asp(O^tBu)-Glu(O^tBu)-Val-Asp(O^tBu)-OH；Ac-Asp(OtBu)(OtBu)-Glu(OtBu)(OtBu)-Val-Asp(OtBu)(OtBu)-OH；(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-[(2-methylpropan-2-yl)oxy]-4-oxobutanoyl]amino]-5-[(2-methylpropan-2-yl)oxy]-5-oxopentanoyl]amino]-3-methylbutanoyl]amino]-4-[(2-methylpropan-2-yl)oxy]-4-oxobutanoic acid
• 化学式: C₃₂H₅₄N₄O₁₂
• 分子量: 686.8
• InChiKey: VFXVGFFIXNERLU-UKDJSQQHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  48
• 可旋转键数：
  22
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  233
• 氢给体数：
  5
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  Ac-Asp(OBu-t)-Glu(OBu-t)-Val-Asp(OBu-t) 在 三溴化磷 、 2-乙氧基-1-乙氧碳酰基-1,2-二氢喹啉 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 15.66h， 生成 C₅₆H₆₆N₉O₁₃⁽¹⁺⁾
  参考文献：
  名称：

  Unimolecular Chemo-fluoro-luminescent Reporter for Crosstalk-Free Duplex Imaging of Hepatotoxicity

  摘要：

  Real-time multiplex imaging is imperative to biology and diagnosis but remains challenging for optical modality. Herein, a unimolecular chemo-fluoro-luminescent reporter (CFR) is synthesized for duplex imaging of drug-induced hepatotoxicity (DIH), a long-term medical concern. CFR simultaneously detects superoxide anion (O-2(center dot)) and caspase-3 (casp3) through respective activation of its independent chemiluminescence and near-infrared fluorescence channels. Such a crosstalk-free duplex imaging capability of CFR enables longitudinal measurement of two correlated biomolecular events (oxidative stress and cellular apoptosis) during the progression of DIH, identifying O-2(center dot) as an earlier biomarker for detection of DIH both in vitro and in vivo. Moreover, CFR detects DIH 17.5 h earlier than histological changes. Thus, our study not only develops a sensitive optical reporter for early detection of DIH but also provides a general molecular design strategy for duplex imaging.

  DOI：

  10.1021/jacs.9b02580

文献信息

• Peptide-Induced AIEgen Self-Assembly: A New Strategy to Realize Highly Sensitive Fluorescent Light-Up Probes
  作者：Aitian Han、Huaimin Wang、Ryan T. K. Kwok、Shenglu Ji、Jun Li、Deling Kong、Ben Zhong Tang、Bin Liu、Zhimou Yang、Dan Ding

  DOI：10.1021/acs.analchem.6b00023

  日期：2016.4.5

  Fluorescent light-up probes with aggregation-induced emission (AIE) characteristics have recently attracted great research interest due to their intelligent fluorescence activation mechanism and excellent photobleaching resistance. In this work, we report a new, simple, and generic strategy to design and prepare highly sensitive AIE fluorescent light-up bioprobe through facile incorporation of a self-assembling

  具有聚集诱导发射（AIE）特性的荧光发光探针由于其智能的荧光激活机制和出色的抗光漂白性，最近引起了极大的研究兴趣。在这项工作中，我们报告了一种新的，简单的，通用的策略，可以通过在识别元件和AIE发光剂（AIEgen）之间轻松整合自组装肽序列GFFY来设计和制备高灵敏度的AIE荧光发光生物探针。生物探针响应靶标后，肽GFFY能够诱导AIEgens的有序自组装，产生紧密和紧密的分子间空间相互作用，从而限制AIEgens的分子内运动，从而实现出色的信号输出。使用两个概念验证，我们已经证明，与没有GFFY诱导的自组装的相比，自组装的掺有肽的AIE发光探针在感应溶液和癌细胞中的相应靶标方面显示出更高的灵敏度。以TPE-GFFYK（DVEDEE-Ac）探针为例，在caspase-3检测中TPE-GFFYK（DVEDEE-Ac）的检测限可低至0.54 pM，远低于TPE-GFFYK（DVEDEE-Ac）的检测限。
• Positron Emission Tomography Imaging of Drug-Induced Tumor Apoptosis with a Caspase-Triggered Nanoaggregation Probe
  作者：Bin Shen、Jongho Jeon、Mikael Palner、Deju Ye、Adam Shuhendler、Frederick T. Chin、Jianghong Rao

  DOI：10.1002/anie.201303422

  日期：2013.9.27

  Drug Design: An 18F‐labeled caspase‐3‐sensitive nanoaggregation positron emission tomography tracer was prepared and evaluated for imaging the caspase‐3 activity in doxorubicin‐treated tumor xenografts. Enhanced retention of the 18F activity in apoptotic tumors is achieved through intramolecular macrocyclization and in situ aggregation upon caspase‐3 activation (see picture).

  药物设计：制备并评估了18 F 标记的 caspase-3 敏感纳米聚集正电子发射断层扫描示踪剂，用于对阿霉素处理的肿瘤异种移植物中的 caspase-3 活性进行成像。通过分子内大环化和 caspase-3 激活后的原位聚集来增强18 F 活性在凋亡肿瘤中的保留（见图）。
• METHODS AND COMPOSITIONS FOR DETECTING OR MEASURING CASPASES OR APOPTOSIS
  申请人：LIFE TECHNOLOGIES CORPORATION

  公开号：US20190309341A1

  公开（公告）日：2019-10-10

  Provided herein are compounds, enzyme substrates, compositions, kits, uses, and methods for detecting the presence or absence of a caspase enzyme, measuring the activity of a caspase enzyme, or detecting the presence or absence of apoptosis. The detection or measurement can occur through intracellular cleavage of a compound or enzyme substrate, which can lead to an increase in fluorescence, e.g., in the violet or red channel, through liberation of a nucleic acid binding dye from a peptide, such as liberation of a DNA-binding dye from a negatively charged peptide comprising a sequence recognized and cleaved by a caspase

  本文提供了用于检测caspase酶的存在或缺失、测量caspase酶活性或检测凋亡的化合物、酶底物、组合物、试剂盒、用途和方法。检测或测量可以通过化合物或酶底物的细胞内裂解进行，这可以通过从肽中释放核酸结合染料（例如从带有被caspase酶识别和裂解的序列的负电荷肽中释放DNA结合染料）来导致荧光增加，例如在紫色或红色通道中。
• CASPASE-TRIGGERED NANO-AGGREGATION PROBES AND METHODS OF USE
  申请人：The Board of Trustees of the Leland Stanford Junior University

  公开号：US20150056137A1

  公开（公告）日：2015-02-26

  Provided is an activatable probe that undergoes intramolecular cyclization and subsequent aggregation in apoptotic tumor cells upon peptidase-initiated, and most advantageously caspase-3, activation. These caspase-sensitive nano-aggregation probes (C-SNAFs) are generally biocompatible, possess NIR spectral properties or may serve as PET or MRI imaging agents, and have a mechanism of target-mediated nanostructure self-assembly amenable to in vivo use. The probes encompass biocompatible condensation chemistry products that comprise D-cysteine and 2-cyano-6-hydroxyquinoline (CHQ) moieties linked to an amino-luciferin scaffold, and which can be activated by a two-step reaction requiring caspase-3/7-mediated cleavage of an aspartate-glutamate-valine-aspartate (L-DEVD) capping peptide and the free intracellular thiol-mediated reduction of the disulfide bond.

  提供的是一种可激活的探针，当肽酶引发并且最好是caspase-3引发时，在凋亡肿瘤细胞中会发生分子内环化和随后的聚集。这些caspase敏感的纳米聚集探针（C-SNAFs）通常具有生物相容性，具有近红外光谱特性或可用作PET或MRI成像剂，并且具有适于体内使用的靶向介导的纳米结构自组装机制。这些探针包括生物相容性凝聚化学产物，其中包括D-半胱氨酸和2-氰基-6-羟基喹啉（CHQ）基团连接到氨基-路西非林支架上，并且可以通过两步反应被激活，需要caspase-3/7介导的天冬氨酸-谷氨酸-缬氨酸-天冬氨酸（L-DEVD）覆盖肽的剪切和游离细胞内硫醇介导的二硫键还原。
• Tailoring a Near‐Infrared Macrocyclization Scaffold Allows the Control of In Situ Self‐Assembly for Photoacoustic/PET Bimodal Imaging
  作者：Yuqi Wang、He Bai、Yinxing Miao、Jianhui Weng、Zheng Huang、Jiayu Fu、Yan Zhang、Jianguo Lin、Deju Ye

  DOI：10.1002/anie.202200369

  日期：2022.3.28

  A near-infrared triazole-IR780 fluorophore was tailored as a PAI-active macrocyclization scaffold for controlling macrocyclization and in situ self-assembly, which enabled the development of a caspase-3-activatable PET/PAI bimodal probe [18F]-IR780-1 for noninvasive imaging of drug-induced tumor apoptosis in vivo, with potential for the early monitoring of tumor response to chemotherapy.

  近红外三唑-IR780荧光团被定制为PAI活性大环化支架，用于控制大环化和原位自组装，从而能够开发caspase-3可激活的PET/PAI双峰探针[ 18 F]-IR780- 1用于体内药物诱导的肿瘤细胞凋亡的无创成像，具有早期监测肿瘤对化疗反应的潜力。