5,8,11,14,17-五氧杂-2-氮杂二十碳二酸 1-(9H-芴-9-基甲基)酯 | 882847-32-7

• 物质功能分类: 生物化工 - 生化试剂 - 氨基酸
• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: 5,8,11,14,17-五氧杂-2-氮杂二十碳二酸 1-(9H-芴-9-基甲基)酯
• 中文别名: 5,8,11,14,17-五氧杂-2-氮杂二十碳二酸1-(9H-芴-9-基甲基)酯
• 英文名称: Fmoc-NH-CH2CH2O-(PEG)4-CH2CH2-COOH
• 英文别名: Fmoc-PEG₅-OH；Fmoc-NHPEG5-COOH；1-(9H-Fluoren-9-yl)-3-oxo-2,7,10,13,16,19-hexaoxa-4-azadocosan-22-oic acid；3-[2-[2-[2-[2-[2-(9H-fluoren-9-ylmethoxycarbonylamino)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]propanoic acid
• CAS: 882847-32-7
• 化学式: C₂₈H₃₇NO₉
• 分子量: 531.603
• InChiKey: TWQTXZPTZPOEEB-UHFFFAOYSA-N

物化性质

• 沸点：
  711.4±60.0 °C(Predicted)
• 密度：
  1.210±0.06 g/cm3 (20 ºC 760 Torr)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  38
• 可旋转键数：
  21
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  122
• 氢给体数：
  2
• 氢受体数：
  9

安全信息

• 海关编码：
  29225090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  存储条件：2-8°C，干燥密封。

制备方法与用途

Fmoc-amino-PEG5-acid 是一种PROTAC连接子，属于PEG类化合物，可用于合成PROTAC分子。

反应信息

• 作为反应物：
  描述：

  5,8,11,14,17-五氧杂-2-氮杂二十碳二酸 1-(9H-芴-9-基甲基)酯 在 哌啶 、 sodium methylate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 67.0h， 生成 6,25-diaza-10,13,16,19,22-pentaoxa-7,26-dioxotritetracontanyl-5-acetamido-3,5-dideoxy-D-glycero-α-D-galacto-2-nonylopyranosylonic acid
  参考文献：
  名称：

  Molecular Wipes: Application to Epidemic Keratoconjuctivitis

  摘要：

  Epidemic keratoconjunctivitis (EKC) is a severe disease of the eye, caused by members of the Adenoviridae (Ad) family, with symptoms such as keratitis, conjunctivitis, pain, edema, and reduced vision that may last for months or years. There are no vaccines or antiviral drugs available to prevent or treat EKC. It was found previously that EKC-causing Ads use sialic acid as a cellular receptor and demonstrated that soluble, sialic acid-containing molecules can prevent infection. In this study, multivalent sialic acid constructs based on 10,12-pentacosadiynoic acid (PDA) have been synthesized, and these constructs are shown to be efficient inhibitors of Ad binding (IC50 = 0.9 mu M) and Ad infectivity (IC50 = 0.7 mu M). The mechanism of action is to aggregate virus particles and thereby prevent them from binding to ocular cells. Such formulations may be used for topical treatment of adenovirus-caused EKC.

  DOI：

  10.1021/jm200545m

文献信息

• [EN] CONJUGATES COMPRISING PEPTIDE GROUPS AND METHODS RELATED THERETO<br/>[FR] CONJUGUÉS COMPRENANT DES GROUPES PEPTIDIQUES ET PROCÉDÉS ASSOCIÉS À CEUX-CI
  申请人：LEGOCHEM BIOSCIENCES INC

  公开号：WO2017089894A1

  公开（公告）日：2017-06-01

  In some aspects, the invention relates to an antibody-drug conjugate, comprising an antibody; a linker; and at least two active agents. In preferred embodiments, the linker comprises a peptide sequence of a plurality of amino acids, and at least two of the active agents are covalently coupled to side chains of the amino acids. The antibody-drug conjugate may comprise a self-immolative group, preferably two-self-immolative groups. The linker may comprise an O-substituted oxime, e.g., wherein the oxygen atom of the oxime is substituted with a group that covalently links the oxime to the active agent; and the carbon atom of the oxime is substituted with a group that covalently links the oxime to the antibody.

  在某些方面，本发明涉及一种抗体药物偶联物，包括：抗体；连接体；以及至少两个活性剂。在优选的实施例中，连接体包括由多个氨基酸组成的肽序列，其中至少两个活性剂通过共价键与氨基酸的侧链连接。抗体药物偶联物可以包括自焚基团，优选地是两个自焚基团。连接体可以包括O-取代的肟，例如，其中肟的氧原子被取代以与活性剂形成共价键连接；肟的碳原子被取代以与抗体形成共价键连接。
• [EN] PBD CONJUGATES FOR TREATING DISEASES<br/>[FR] CONJUGUÉS DE PBD POUR LE TRAITEMENT DE MALADIES
  申请人：ENDOCYTE INC

  公开号：WO2017172930A1

  公开（公告）日：2017-10-05

  The present disclosure relates to pyrrolobenzodiazepine (PBD) prodrugs and conjugates thereof. The present disclosure also relates to pharmaceutical compositions of the conjugates described herein, methods of making and methods of using the same.

  本公开涉及吡咯并苯二氮卓（PBD）前药及其共轭物。本公开还涉及所述共轭物的药物组合物，以及制造和使用它们的方法。
• [EN] ADRENOMEDULLIN-ANALOGUES FOR LONG-TERM STABILIZATION AND THEIR USE<br/>[FR] ANALOGUES D'ADRÉNOMÉDULLINE POUR STABILISATION À LONG TERME ET LEUR UTILISATION
  申请人：BAYER AG

  公开号：WO2020254197A1

  公开（公告）日：2020-12-24

  The invention relates to stabilized Adrenomedullin derivatives and use thereof. In particular, the invention relates to novel, biologically active, stabilized Adrenomedullin (ADM) compounds. The invention further relates to the compounds for use in a method for the treatment and/or prevention of diseases, especially of cardiovascular, edematous and/or inflammatory disorders, and to medicaments comprising the compounds for treatment and/or prevention of cardiovascular, edematous and/or inflammatory disorders.

  该发明涉及稳定的肾上腺髓质素衍生物及其用途。具体而言，该发明涉及新型、具有生物活性的稳定肾上腺髓质素（ADM）化合物。该发明进一步涉及用于治疗和/或预防疾病的方法中的化合物，特别是心血管、水肿和/或炎症性疾病，以及包含该化合物的药物，用于治疗和/或预防心血管、水肿和/或炎症性疾病。
• Site‐Selective Cysteine–Cyclooctyne Conjugation
  作者：Chi Zhang、Peng Dai、Alexander A. Vinogradov、Zachary P. Gates、Bradley L. Pentelute

  DOI：10.1002/anie.201800860

  日期：2018.5.28

  tags, and cytotoxic drug molecules. Fusion of DBCO‐tag with the protein of interest enables regioselective cysteine modification on proteins that contain multiple endogenous cysteines; these examples include green fluorescent protein and the antibody trastuzumab. This study demonstrates that short peptide tags can aid in accelerating bond‐forming reactions that are often slow to non‐existent in water

  我们报告了在肽或蛋白质的N或C末端的七个残基肽标签（DBCO标签，Leu-Cys-Tyr-Pro-Trp-Val-Tyr）与多种肽之间的定点半胱氨酸-环辛炔偶联反应氮杂二苯并环辛炔（DBCO）试剂。与半胱氨酸肽对照相比，DBCO标签可将硫醇-yne反应速率提高220倍，从而使DBCO标签与DBCO连接的荧光探针，亲和标签和细胞毒性药物分子选择性结合。DBCO-tag与目标蛋白的融合可对包含多个内源性半胱氨酸的蛋白进行区域选择性的半胱氨酸修饰；这些例子包括绿色荧光蛋白和曲妥珠单抗抗体。这项研究表明，短肽标签可以帮助加速在水中缓慢至不存在的成键反应。
• Design, synthesis, and biological characterization of novel PEG-linked dimeric modulators for CXCR4
  作者：Yilei Yang、Mei Gao、Qinghao Zhang、Chaozai Zhang、Xiaohong Yang、Ziwei Huang、Jing An

  DOI：10.1016/j.bmc.2016.08.062

  日期：2016.11

  been widely demonstrated both biologically and structurally. This paper mainly focused on the development of structure-based dimeric ligands that target CXCL12–CXCR4 interaction and signaling. This study presents the design and synthesis of a series of [PEG]n linked dimeric ligands of CXCR4 based on the knowledge of the homodimeric crystal structure of CXCR4 and our well established platform of chemistry

  CXCR4二聚化已在生物学和结构上得到了广泛证明。本文主要关注针对CXCL12–CXCR4相互作用和信号传导的基于结构的二聚体配体的开发。这项研究基于对CXCR4的同二聚体晶体结构的了解以及我们为CXCR4建立的化学和生物测定平台，提出了一系列CXCR4的[PEG] n连接的二聚配体的设计和合成。这些新的配体包括由两个DV3衍生的部分组成的[PEG] n连接的同二聚体或异二聚体肽（其中DV3是vMIP-II的1-10（V3）残基的N末端模块的All- d-氨基酸类似物）或DV3部分和CXCL12 1 – 8的混合体。在总共24种肽配体中，四种拮抗剂和三种激动剂表现出良好的CXCR4结合亲和力，IC 50值分别<50 nM和<800 nM。用SUP-T1细胞进行的趋化性和钙动员试验进一步确定了CXCR4的两个有前途的先导调节剂：配体4，一种[PEG 3 ] 2连接的同型二聚体DV3，是一种有效的CXCR4拮抗剂（IC