生物素-PEG12-羧酸 | 1085704-04-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 生物素及其衍生物
• 中文名称: 生物素-PEG12-羧酸
• 英文名称: O-[2-(biotinylamino)ethyl]-O'-(2-carboxyethyl)undecaethylene glycol
• 英文别名: Biotin-PEG12-Acid；3-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]propanoic acid
• CAS: 1085704-04-6
• 化学式: C₃₇H₆₉N₃O₁₆S
• 分子量: 844.031
• InChiKey: AEMUKWXFLKZKMD-UEMWQVMZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.2
• 重原子数：
  57
• 可旋转键数：
  44
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  244
• 氢给体数：
  4
• 氢受体数：
  17

反应信息

• 作为反应物：
  描述：

  (S)-di-tert-butyl 2-(3-((S)-6-(benzylamino)-1-(tert-butoxy)-1-oxohexan-2-yl)ureido)pentane-1,5-dioate 、 生物素-PEG12-羧酸 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.25h， 生成
  参考文献：
  名称：

  Rational design of urea-based glutamate carboxypeptidase II (GCPII) inhibitors as versatile tools for specific drug targeting and delivery

  摘要：

  Glutamate carboxypeptidase II (GCPII), also known as prostate specific membrane antigen (PSMA), is an established prostate cancer marker and is considered a promising target for specific anticancer drug delivery. Low-molecular-weight inhibitors of GCPII are advantageous specific ligands for this purpose. However, they must be modified with a linker to enable connection of the ligand with an imaging molecule, anticancer drug, and/or nanocarrier. Here, we describe a structure-activity relationship (SAR) study of GCPII inhibitors with linkers suitable for imaging and drug delivery. Structure-assisted inhibitor design and targeting of a specific GCPII exosite resulted in a 7-fold improvement in Ki value compared to the parent structure. X-ray structural analysis of the inhibitor series led to the identification of several inhibitor binding modes. We also optimized the length of the inhibitor linker for effective attachment to a biotin-binding molecule and showed that the optimized inhibitor could be used to target nanoparticles to cells expressing GCPII.

  DOI：

  10.1016/j.bmc.2014.05.061

文献信息

• [EN] KETONE INHIBITORS OF LYSINE GINGIPAIN<br/>[FR] INHIBITEURS CÉTONE DE LYSINE GINGIPAÏNE
  申请人：CORTEXYME INC

  公开号：WO2018053353A1

  公开（公告）日：2018-03-22

  The present invention provides compounds according to Formula (I) as described herein, and their use for inhibiting the lysine gingipain protease (Kgp) from the bacterium Porphyromonas gingivalis. Also described are gingipain activity probe compounds and methods for assaying gingipain activity are also described, as well as methods for the treatment of disorders associated with P. gingivalis infection, including brain disorders such as Alzheimer's disease.

  本发明提供了如下式（I）所述的化合物，以及它们用于抑制牙龈假单胞菌（Porphyromonas gingivalis）的赖氨酸基因底物蛋白酶（Kgp）的用途。还描述了牙龈蛋白酶活性探针化合物和测定牙龈蛋白酶活性的方法，以及用于治疗与牙龈假单胞菌感染相关的疾病的方法，包括阿尔茨海默病等脑部疾病。
• Protein-mediated dethreading of a biotin-functionalised pseudorotaxane
  作者：Stuart T. Caldwell、Catherine Maclean、Mathis Riehle、Alan Cooper、Margaret Nutley、Gouher Rabani、Brian Fitzpatrick、Vincent M. Rotello、Brian O. Smith、Belal Khaled、Patrice Woisel、Graeme Cooke

  DOI：10.1039/c3ob41612g

  日期：——

  In this article, we describe the synthesis of new biotin-functionalised naphthalene derivatives 3 and 4 and their complexation behaviour with avidin and neutravidin using a range of analytical techniques. We have shown using 2-(4′-hydroxyazobenzene)benzoic acid displacement and ITC experiments, that compounds 3 and 4 have the propensity to form reasonably high-affinity bioconjugates with avidin and neutravidin. We have also demonstrated using 1H NMR, UV-vis and fluorescence spectroscopy that the naphthalene moiety of 3 and 4 facilitates the formation of pseudorotaxane-like structures with 1 in water. We have then investigated the ability of avidin and neutravidin to modulate the complexation between 1 and 3 or 4. UV-vis and fluorescence spectroscopy has shown that in both cases the addition of the protein disrupts complexation between the naphthalene moieties of 3 and 4 with 1.

  在本文中，我们介绍了新的生物素功能化萘衍生物 3 和 4 的合成及其与阿维丁和中性阿维丁的络合行为，并使用了一系列分析技术。我们利用 2-（4′-羟基偶氮苯）苯甲酸置换和 ITC 实验表明，化合物 3 和 4 具有与阿维丁和中性阿维丁形成合理的高亲和性生物结合体的倾向。我们还利用 1H-核磁共振、紫外-可见光和荧光光谱证明，3 和 4 中的萘基有助于在水中与 1 形成类似假紫杉醇的结构。我们随后研究了阿维丁和中性阿维丁调节 1 与 3 或 4 之间复合物的能力。紫外-可见光谱和荧光光谱显示，在这两种情况下，蛋白质的加入都会破坏 3 和 4 的萘基与 1 的复合物。
• Compositions and methods for targeted cytokine delivery
  申请人：Washington University

  公开号：US10793613B2

  公开（公告）日：2020-10-06

  The present disclosure encompasses compositions and methods for targeted cytokine delivery. The compositions disclosed herein comprise a cytokine linked to a ligand and may improve immunotherapy by limiting side effects associated with immunotherapy.

  本公开包括用于靶向细胞因子递送的组合物和方法。本文公开的组合物包括与配体相连的细胞因子，可通过限制与免疫疗法相关的副作用来改善免疫疗法。
• Structure-Based Discovery of High-Affinity Small Molecule Ligands and Development of Tool Probes to Study the Role of Chitinase-3-Like Protein 1
  作者：Wojciech Czestkowski、Łukasz Krzemiński、Michał C. Piotrowicz、Marzena Mazur、Elżbieta Pluta、Gleb Andryianau、Robert Koralewski、Krzysztof Matyszewski、Sylwia Olejniczak、Michał Kowalski、Katarzyna Lisiecka、Rafał Kozieł、Katarzyna Piwowar、Diana Papiernik、Marcin Nowotny、Agnieszka Napiórkowska-Gromadzka、Elżbieta Nowak、Dorota Niedziałek、Grzegorz Wieczorek、Anna Siwińska、Tomasz Rejczak、Karol Jędrzejczak、Krzysztof Mulewski、Jacek Olczak、Zbigniew Zasłona、Adam Gołębiowski、Katarzyna Drzewicka、Agnieszka Bartoszewicz

  DOI：10.1021/acs.jmedchem.3c02255

  日期：2024.3.14

  molecules in binding between CHI3L1 and biotinylated small molecules or heparan sulfate-based probes. Small molecule binders of YKL-40 were identified in our chitotriosidase inhibitors library with MST and confirmed through X-ray crystallography. Based on cocrystal structures of potent hit compounds with CHI3L1, small molecule probes 19 and 20 were designed for an AS assay. Structure-based optimization

  Chitinase-3-like-1 (CHI3L1)，也称为 YKL-40，是一种与炎症、纤维化和癌症相关的糖蛋白。本研究利用微尺度热泳 (MST) 和 AlphaScreen (AS) 探索了 CHI3L1 与各种寡糖的相互作用。这些研究指导了高通量筛选测定的开发，以评估小分子对 CHI3L1 与生物素化小分子或基于硫酸乙酰肝素的探针之间结合的干扰。 YKL-40 的小分子结合物在我们的壳三糖苷酶抑制剂库中通过 MST 进行了鉴定，并通过 X 射线晶体学进行了确认。基于强效命中化合物与 CHI3L1 的共晶结构，小分子探针19和20被设计用于 AS 测定。基于结构的优化使化合物30和31具有纳摩尔活性和药物样特性。此外，还开发了一种使用生物素化硫酸乙酰肝素作为探针的正交 AS 测定法。两种测定中化合物的亲和力均显示出显着的相关性。这些筛选工具和化合物为研究 CHI3L1 的作用提供了新途径。
• COMPOSITIONS AND METHODS FOR TARGETED CYTOKINE DELIVERY
  申请人：Washington University

  公开号：EP3233192B1

  公开（公告）日：2021-04-14