| 1272378-29-6

• 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
• CAS: 1272378-29-6
• 化学式: C₄₅H₈₉N₁₅O₇
• 分子量: 952.298
• InChiKey: GTYBMRIWTLMGCF-CXWHUAPYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.13
• 重原子数：
  67.0
• 可旋转键数：
  42.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  411.86
• 氢给体数：
  15.0
• 氢受体数：
  15.0

反应信息

• 作为产物：
  描述：

  tert-butyl N-[(2S)-1-[[(2S)-1-[[(2S)-6-[[(2S)-2,6-bis[[(2S)-2,6-bis[(2-methylpropan-2-yl)oxycarbonylamino]hexanoyl]amino]hexanoyl]amino]-1-oxo-1-(prop-2-ynylamino)hexan-2-yl]amino]-6-[[(2S)-2,6-bis[(2-methylpropan-2-yl)oxycarbonylamino]hexanoyl]amino]-1-oxohexan-2-yl]amino]-6-[(2-methylpropan-2-yl)oxycarbonylamino]-1-oxohexan-2-yl]carbamate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以92%的产率得到
  参考文献：
  名称：

  Peptide Dendrons as Thermal-Stability Amplifiers for Immunoglobulin G1 Monoclonal Antibody Biotherapeutics

  摘要：

  生物治疗药物如单克隆抗体（mAbs）在制药行业中占据重要份额，主要用于治疗癌症、皮肤疾病和免疫系统疾病等危及生命的慢性疾病。聚集、断裂、氧化和还原等不稳定性导致这些产品通常需要在低温（-80至-20°C）下储存。然而，在这些温度下可靠存储面临挑战，尤其是在发展中国家和欠发达国家。因此，最近人们对开发能够在较高温度（25至55°C）下保持稳定的配方产生了新的兴趣。大多数治疗性配方中含有盐、糖、氨基酸、表面活性剂和聚合物等辅料，以提供生物治疗药物的稳定性，但它们在高温下的有效性有限。本研究提出使用不同代际的肽树突状体来创建高温稳定的配方。在这些树突状体中，第三代赖氨酸树突状体L6被确定为提供对mAbs最高稳定性的材料，相关的分析技术如尺寸排阻色谱（SEC）、动态光散射（DLS）、纳米颗粒追踪分析（NTA）和圆二色谱（CD）均进行了验证。通过溶血活性测试确认了这些树突状体的生物相容性。通过基于表面等离子共振（SPR）的活性测定确认了树突状体与mAb活性之间不存在干扰。我们希望这项研究能促使人们利用这种高代树突状体来增强mAbs的热稳定性。

  DOI：

  10.1021/acs.bioconjchem.7b00389

文献信息

• [EN] A FORMULATION FOR STABILIZING BIO-THERAPEUTICS<br/>[FR] FORMULATION POUR LA STABILISATION D'AGENTS BIOLOGIQUES THÉRAPEUTIQUES
  申请人：INDIAN INSTITUTE TECH DELHI

  公开号：WO2018096552A1

  公开（公告）日：2018-05-31

  The present disclosure relates to a formulation comprising: a) a dendron of Formula I; b) at least one bio-therapeutic; c) at least one buffer; and d) at least one salt, wherein the bio-therapeutic to dendron molar ratio is in the range of 1:0.5-1:3. The dendron stabilizes the bio-therapeutic in the formulation at a temperature of up to 55 °C.

  本公开涉及一种配方，包括：a) 公式I的树状分子；b) 至少一种生物治疗药物；c) 至少一种缓冲剂；和d) 至少一种盐，其中生物治疗药物与树状分子的摩尔比在1:0.5至1:3的范围内。树状分子可以在高达55°C的温度下稳定配方中的生物治疗药物。
• Tailoring the Supramolecular Structure of Guanidinylated Pullulan toward Enhanced Genetic Photodynamic Therapy
  作者：Jie Zhou、Aisha Roshan Mohamed Wali、Shengnan Ma、Yiyan He、Dong Yue、James Zhenggui Tang、Zhongwei Gu

  DOI：10.1021/acs.biomac.8b00273

  日期：2018.6.11

  In the progress of designing a gene carrier system, what is urgently needed is a balance of excellent safety and satisfactory efficiency. Herein, a straightforward and versatile synthesis of a cationic guanidine-decorated dendronized pullulan (OGG3P) for efficient genetic photodynamic therapy was proposed. OGG3P was able to block the mobility of DNA from a weight ratio of 2. However, G3P lacking guanidine residues could not block DNA migration until at a weight ratio of 15, revealing guanidination could facilitate DNA condensation via specific guanidinium-phosphate interactions. A zeta potential plateau (∼+23 mV) of OGG3P complexes indicated the nonionic hydrophilic hydroxyl groups in pullulan might neutralize the excessive detrimental cationic charges. There was no obvious cytotoxicity and hemolysis, but also enhancement of transfection efficiency with regard to OGG3P in comparison with that of native G3P in Hela and HEK293T cells. More importantly, we found that the uptake efficiency in Hela cells between OGG3P and G3P complexes was not markedly different. However, guanidination caused changes in uptake pathway and led to macropinocytosis pathway, which may be a crucial reason for improved transfection efficiency. After introducing a therapeutic pKillerRed-mem plasmid, OGG3P complexes achieved significantly enhanced KillerRed protein expression and ROS production under irradiation. ROS-induced cancer cells proliferation suppression was also confirmed. This study highlights the guanidine-decorated dendronized pullulan could emerge as a reliable nonviral gene carrier to specifically deliver therapeutic genes.

  在设计基因载体系统的过程中，迫切需要兼顾出色的安全性和令人满意的效率。本文提出了一种用于高效基因光动力疗法的阳离子胍装饰树枝化拉鲁兰（OGG3P）的直接、多功能合成方法。然而，缺乏胍残基的 G3P 在重量比为 15 时才能阻止 DNA 迁移，这表明胍化可通过特定的胍-磷酸相互作用促进 DNA 凝聚。OGG3P 复合物的 zeta 电位高原（∼+23 mV）表明，拉普兰中的非离子亲水羟基可以中和过多的有害阳离子电荷。与原生 G3P 相比，OGG3P 在 Hela 和 HEK293T 细胞中没有明显的细胞毒性和溶血现象，而且还提高了转染效率。更重要的是，我们发现 OGG3P 和 G3P 复合物在 Hela 细胞中的吸收效率没有明显差异。然而，鸟苷酸化引起了摄取途径的改变，并导致了大吞噬途径，这可能是提高转染效率的关键原因。引入治疗性 pKillerRed-mem 质粒后，OGG3P 复合物在辐照条件下显著增强了 KillerRed 蛋白的表达和 ROS 的产生。ROS 诱导的癌细胞增殖抑制也得到了证实。这项研究表明，胍基装饰的树枝化拉鲁兰可以作为一种可靠的非病毒基因载体，特异性地传递治疗基因。
• Gelation and topochemical polymerization of peptide dendrimers
  作者：V. Haridas、Yogesh K. Sharma、Rhiannon Creasey、Srikanta Sahu、Christopher T. Gibson、Nicolas H. Voelcker

  DOI：10.1039/c0nj00544d

  日期：——

  A new class of peptide-based dendrons and dendrimers is presented that display unique vesicle-driven organogelation. We demonstrate the crosslinking of diacetylene-based dendrimers in the gel state, producing strongly fluorescent polydiacetylenes. The crosslinked gels crafted from peptide dendrimers may find practical use in various applications, including as scaffold materials in tissue engineering and for drug delivery.

  本文介绍了一类新型肽基树枝和树枝状聚合物，它们显示出独特的囊泡驱动有机凝胶化作用。我们展示了二乙炔基树枝状聚合物在凝胶状态下的交联，从而产生了强荧光聚二乙炔。由多肽树枝状聚合物制成的交联凝胶可用于各种实际用途，包括组织工程中的支架材料和药物输送。
• Designer peptide dendrimers using click reaction
  作者：V. Haridas、Yogesh K. Sharma、Srikanta Sahu、Ram P. Verma、Sandhya Sadanandan、Bharat G. Kacheshwar

  DOI：10.1016/j.tet.2011.01.023

  日期：2011.3

  We designed and synthesized various peptide dendrimers using a 1,3-dipolar cycloaddition (Click) reaction. The dendritic structures reported here include symmetrical, asymmetrical, and cationic dendrimers with triazole, cystine, aromatic, aliphatic, and Lys-Asp dipeptide cores. The high chemoselectivity of the click reaction allowed us to synthesize good yields of high-purity protected and unprotected dendritic structures. Triazole is an excellent peptide bond mimic, which remains hydrolytically stable. Dendrimer 15a and the core unit 21 gelate in a mixture of organic solvents. We also demonstrated the versatility of the design by synthesizing various carbohydrate-based dendrimers. (C) 2011 Elsevier Ltd. All rights reserved.