Fmoc-Lys(ClZ)-OH

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: Fmoc-Lys(ClZ)-OH
• 英文别名: Fmoc-Lys(2-Cl-Z)-OH；(2S)-6-[(2-chlorophenyl)methoxycarbonylamino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)hexanoic acid
• 化学式: C₂₉H₂₉ClN₂O₆
• mdl: MFCD00065664
• 分子量: 537.012
• InChiKey: VUEYAXRHPZGZOL-SANMLTNESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  38
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.275
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Fmoc-Lys(ClZ)-OH 在 三氟甲磺酸 、 茴香硫醚 、 三氟乙酸 作用下， 反应 1.0h， 以83.6%的产率得到FMOC-赖氨酸
  参考文献：
  名称：

  一种合成长链磷酸肽的新实用策略。

  摘要：

  已经开发出用于合成长链磷酸肽的新的实用策略。Lys的2-氯苄氧基羰基（CIZ）基团和磷氨基酸的甲基（Me）均完好无损，而其他常用的侧链保护基在使用高酸性三氟甲磺酸（TFMSA）的试剂反应期间被定量裂解。系统（高TFMSA：TFMSA-TFA-m-cresol = 1：9：1，v / v）。用高TFMSA对含CIZ和Me基团的受保护的磷肽树脂进行选择性脱保护，得到部分受保护的磷肽片段，适用于硫酯介导的片段缩合。还开发了9-芴基甲氧羰基（Fmoc）基团的脱保护方案，该方案可避免对受保护的磷酸氨基酸产生明显的副反应。

  DOI：

  10.1248/cpb.48.1230

文献信息

• Orally Active Peptidic Bradykinin B1 Receptor Antagonists Engineered from a Cyclotide Scaffold for Inflammatory Pain Treatment
  作者：Clarence T. T. Wong、Dewi K. Rowlands、Chi-Hang Wong、Theodore W. C. Lo、Giang K. T. Nguyen、Hoi-Yeung Li、James P. Tam

  DOI：10.1002/anie.201200984

  日期：2012.6.4

  Edible: By grafting natural peptide antagonists onto the cyclotide kalata B1, orally active peptides were engineered, which are potentially useful therapeutics for the treatment of inflammatory pain. For example, the entire loop 6 of kalata B1 was replaced with the peptidic bradykinin B1 receptor antagonist DALK (red in scheme) to obtain the cyclic bradykinin antagonist ckb‐kal.

  食用：通过将天然肽拮抗剂移植到环肽kalata B1上，可设计出口服活性肽，这对于治疗炎性疼痛可能是有用的疗法。例如，用肽缓激肽B 1 受体拮抗剂DALK（方案中为红色）代替了卡拉塔B1的整个环6，以获得环状缓激肽拮抗剂ckb‐kal。
• Selective Substrates and Activity-Based Probes for Imaging of the Human Constitutive 20S Proteasome in Cells and Blood Samples
  作者：Wioletta Rut、Marcin Poręba、Paulina Kasperkiewicz、Scott J. Snipas、Marcin Drąg

  DOI：10.1021/acs.jmedchem.8b00026

  日期：2018.6.28

  the HyCoSuL approach, we designed and synthesized novel and selective fluorogenic substrates for each of these three constitutive 20S proteasome activities and applied them to assess inhibition of proteasome subunits by MG-132 and a clinically used inhibitor bortezomib. Our results confirm the utility of designed substrates in biochemical assays. Furthermore, selective peptide sequences obtained in this

  蛋白酶体是维持蛋白质稳态的关键酶复合物。蛋白酶体功能紊乱导致包括癌症，自身免疫和神经退行性疾病在内的病理。因此，蛋白酶体构成药物开发的极好的分子靶标。在这里，我们使用HyCoSuL方法为这三个20S组成型蛋白酶体活性中的每一个设计和合成了新颖的选择性荧光底物，并将它们应用于评估MG-132和临床使用的硼替佐米对蛋白酶体亚基的抑制作用。我们的结果证实了设计的底物在生化分析中的实用性。此外，以此方式获得的选择性肽序列用于构建荧光团标记的基于活性的探针，然后用于同时检测HEK-293F细胞和红细胞裂解液中的每个20S组成型蛋白酶体亚基。总体而言，我们描述了一种简单而快速的方法，可用于测量全血样本中20S组成型蛋白酶体的活性，该方法可以早期诊断与异常上调的蛋白酶体活性有关的病理状态。
• Development of Cyclic NGR Peptides with Thioether Linkage: Structure and Dynamics Determining Deamidation and Bioactivity
  作者：Kata Nóra Enyedi、András Czajlik、Krisztina Knapp、András Láng、Zsuzsa Majer、Eszter Lajkó、László Kőhidai、András Perczel、Gábor Mező

  DOI：10.1021/jm501630j

  日期：2015.2.26

  interest, in particular due to their potential applications in drug targeting. Here we report the synthesis and structural analysis of novel thioether bond-linked cyclic NGR peptides. Our results show that their chemostability (resistance against spontaneous decomposition forming isoAsp and Asp derivatives) strongly depends on both sample handling conditions and structural properties. A significant correlation

  识别肿瘤新脉管系统中CD13受体的NGR肽备受关注，特别是由于其在药物靶向中的潜在应用。在这里我们报告了新型硫醚键连接的环状NGR肽的合成和结构分析。我们的结果表明，它们的化学稳定性（抵抗形成异Asp和Asp衍生物的自发分解的能力）在很大程度上取决于样品处理条件和结构性质。发现化学稳定性与结构度量之间存在显着相关性，例如NH Gly –CO Asn-sc距离。Asn的侧链取向是关键的决定因素。如果它远离HN Gly，化学稳定性增加。结构稳定因子（例如，氢键）降低了它们的内部动力学，因此生物分子对自发分解的抵抗力甚至更高。在A2058黑色素瘤细胞系中检查了环状NGR肽对细胞粘附的影响。发现一些研究的肽具有长期特征逐渐增加了细胞粘附，表明负责粘附诱导作用的整联蛋白结合iso Asp衍生物的时间依赖性形成。
• Peptide conjugates of 4-aminocyclophosphamide as prodrugs of phosphoramide mustard for selective activation by prostate-specific antigen (PSA)
  作者：Yongying Jiang、Longqin Hu

  DOI：10.1016/j.bmc.2013.09.039

  日期：2013.12

  In our continued effort to develop prodrugs of phosphoramide mustard, conjugates of 4-aminocyclophosphamide (4-NH2-CPA) with three PSA-specific peptides were synthesized and evaluated as substrates of PSA. These include conjugates of cis-(2R,4R)-4-NH2-CPA with a tetrapeptide Succinyl-Ser-Lys-Leu-Gln-OH, a hexapeptide Succinyl-His-Ser-Ser-Lys-Leu-Gln-OH, and a pentapeptide Glutaryl-Hyp-Ala-Ser-Chg-Gln-OH. These conjugates were cleaved by PSA efficiently and exclusively after the expected glutamine residue to release 4-NH2-CPA, the activated prodrug form of phosphoramide mustard. The cleavage was most efficient for the pentapeptide conjugate 3 (Glutaryl-Hyp-Ala-Ser-Chg-Gln-NH-CPA), which showed a half-life of 55 min with PSA, followed by the hexapeptide conjugate 2 (Succinyl-His-Ser-Ser-Lys-Leu-Gln-NH-CPA) and the tertrapeptide conjugate 1 (Succinyl-Ser-Lys-Leu-Gln-NH-CPA) with half-lives of 6.5 and 12 h, respectively. These results indicate a potential of the conjugate 3 as an anticancer prodrug of phosphoramide mustard for selective PSA activation. (C) 2013 Elsevier Ltd. All rights reserved.
• Design and synthesis of Hsp90 inhibitors: Exploring the SAR of Sansalvamide A derivatives
  作者：Robert P. Sellers、Leslie D. Alexander、Victoria A. Johnson、Chun-Chieh Lin、Jeremiah Savage、Ricardo Corral、Jason Moss、Tim S. Slugocki、Erinprit K. Singh、Melinda R. Davis、Suchitra Ravula、Jamie E. Spicer、Jenna L. Oelrich、Andrea Thornquist、Chung-Mao Pan、Shelli R. McAlpine

  DOI：10.1016/j.bmc.2010.07.042

  日期：2010.9

  Utilizing the structure-activity relationship we have developed during the synthesis of the first two generations and mechanism of action studies that point to the interaction of these molecules with the key oncogenic protein Hsp90, we report here the design of 32 new Sansalvamide A derivatives and their synthesis. Our new structures, designed from previously reported potent compounds, were tested for cytotoxicity on the HCT116 colon cancer cell line, and their binding to the biological target was analyzed using computational studies involving blind docking of derivatives using Autodock. Further, we show new evidence that our molecules bind directly to Hsp90 and modulate Hsp90's binding with client proteins. Finally, we demonstrate that we have integrated good ADME properties into a new derivative. Published by Elsevier Ltd.