3-(N-methacryloylglycylglycyl)thiazolidine-2-thione | 873443-48-2

• 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: 3-(N-methacryloylglycylglycyl)thiazolidine-2-thione
• 英文别名: N-methacryloylglycylglycyl-thiazolidine-2-thione；2-methyl-N-[2-oxo-2-[[2-oxo-2-(2-sulfanylidene-1,3-thiazolidin-3-yl)ethyl]amino]ethyl]prop-2-enamide
• CAS: 873443-48-2
• 化学式: C₁₁H₁₅N₃O₃S₂
• 分子量: 301.39
• InChiKey: WTNNCZWVDRDBPY-UHFFFAOYSA-N

物化性质

• 熔点：
  82-84 °C(Solv: ethyl acetate (141-78-6))
• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  136
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-巯基噻唑啉 、 2-[[2-(2-甲基丙-2-烯酰氨基)乙酰基]氨基]乙酸 在 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 3-(N-methacryloylglycylglycyl)thiazolidine-2-thione
  参考文献：
  名称：

  Multi-component Polymeric System for Tumour Cell-Specific Gene Delivery Using a Universal Bungarotoxin Linker

  摘要：

  使用了一种新的通用工具，通过特定的、非共价的和非破坏性的附着方式，将重组抗体片段连接到聚合物修饰的腺病毒上，以调控腺病毒基因传递载体的趋向性。我们制备了一种多价反应性N-（2-羟丙基）甲基丙烯酰胺基共聚物（PHPMA），该共聚物带有α-金环蛇毒素结合肽（BTXbp）。该共聚物被用于腺病毒载体（Ad）的共价表面修饰。α-金环蛇毒素蛋白（BTX）对BTXbp具有纳摩尔级别的结合亲和力，从而可以实现BTX融合蛋白的非共价连接。携带BTX的抗PSMA抗体单链可变片段（scFv-BTX）与前列腺特异性膜抗原（PSMA）结合，并通过共聚物包被的腺病毒与之偶联，使得腺病毒能够通过PSMA受体特异性地感染前列腺癌细胞。如ELISA所示，经共聚物包被的病毒与抗Ad抗体的结合能力显著降低。与未经修饰的Ad相比，共聚物包被的Ad对PC-3和LNCaP前列腺癌细胞的感染效率降低了约100倍。在PSMA阳性LNCaP细胞中，scFv-BTX与Ad-PHPMA-BTXbp的偶联使得感染效率恢复至5-10倍。在PSMA阴性的PC-3细胞中，scFv-BTX与Ad-PHPMA-BTXbp的偶联对感染效率没有提升。我们已经证明，所提出的Ad-PHPMA-BTXbp/scFv-BTX系统可以作为一种用于受体特异性病毒治疗的通用工具。

  DOI：

  10.1007/s11095-010-0088-8

文献信息

• HPMA copolymer-doxorubicin conjugates: The effects of molecular weight and architecture on biodistribution and in vivo activity
  作者：Tomáš Etrych、Vladimír Šubr、Jiří Strohalm、Milada Šírová、Blanka Říhová、Karel Ulbrich

  DOI：10.1016/j.jconrel.2012.06.029

  日期：2012.12

  of soluble polymer drug carriers significantly influence the biodistribution and anti‐tumour activities of their doxorubicin (DOX) conjugates in tumour-bearing mice. Biodistribution of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-DOX conjugates of linear and star architectures were compared in EL4 T-cell lymphoma-bearing mice. Biodistribution, including tumour accumulation, and anti‐tumour activity

  可溶性聚合物药物载体的分子量和分子结构显着影响其阿霉素（DOX）缀合物在荷瘤小鼠中的生物分布和抗肿瘤活性。在带有EL4 T细胞淋巴瘤的小鼠中比较了线性和星形结构的N-（2-羟丙基）甲基丙烯酰胺（HPMA）共聚物-DOX共轭物的生物分布。结合物的生物分布，包括肿瘤积累和抗肿瘤活性，在很大程度上取决于结合物的分子量（MW），多分散性，流体动力学半径（R h）和分子结构。随着分子量的增加，肾清除率降低，并且缀合物显示出延长的血液循环和增强的肿瘤蓄积。具有柔性聚合物链的线性共轭物比具有相当分子量的高度分支的星形共轭物通过肾脏清除的速度更快。有趣的是，数据提示星形和线性缀合物的肾脏滤过机制不同。唯一的星缀合物具有低于50000 g.mo兆瓦 -1通过肾脏过滤除去，同时用兆瓦线性聚合物缀合物近70000 g.mol - 1注射后36–96 h尿液中检测到超过了公认的肾脏消除极限。另外，荷瘤小鼠的存活强
• POLYMERIC DRUG DELIVERY CONJUGATES AND METHODS OF MAKING AND USING THEREOF
  申请人：Kopecková Pavla

  公开号：US20130156722A1

  公开（公告）日：2013-06-20

  Described herein are biodegradable drug delivery conjugates for effectively delivering bioactive agents to a subject. The drug delivery conjugates comprise a water-soluble high molecular weight linear biodegradable polymer backbone comprising a plurality of linear water-soluble polymeric segments connected to one another by a first (main-chain) cleavable linker, wherein a bioactive agent is covalently bonded to at least one water-soluble polymeric segment, at least one cleavable linker, or a combination thereof. The conjugates possess numerous advantages over prior art delivery conjugates. Also described herein are methods for making and using the conjugates.

  本文描述了一种可生物降解的药物传递共轭物，用于有效地将生物活性物质传递给受试者。药物传递共轭物包括水溶性高分子量线性可生物降解聚合物骨架，该骨架包括通过第一（主链）可断裂连接剂相互连接的多个线性水溶性聚合物段，其中生物活性物质与至少一个水溶性聚合物段，至少一个可断裂连接剂或其组合共价键合。与先前的传递共轭物相比，这些共轭物具有许多优点。本文还描述了制备和使用这些共轭物的方法。
• Polymeric drug delivery conjugates and methods of making and using thereof
  申请人：Pan Huaizhong

  公开号：US09289510B2

  公开（公告）日：2016-03-22

  Described herein are biodegradable drug delivery conjugates for effectively delivering bioactive agents to a subject. The drug delivery conjugates comprise a water-soluble high molecular weight linear biodegradable polymer backbone comprising a plurality of linear water-soluble polymeric segments connected to one another by a first (main-chain) cleavable linker, wherein a bioactive agent is covalently bonded to at least one water-soluble polymeric segment, at least one cleavable linker, or a combination thereof. The conjugates possess numerous advantages over prior art delivery conjugates. Also described herein are methods for making and using the conjugates.

  本文描述了一种生物可降解的药物传递共轭物，用于有效地将生物活性物质传递给受体。该药物传递共轭物包含一个水溶性高分子量线性生物可降解聚合物骨架，该骨架由多个线性水溶性聚合物段通过第一（主链）可断链连接在一起，其中生物活性物质与至少一个水溶性聚合物段、至少一个可断链连接或两者的组合共价键合。与先前的传递共轭物相比，这些共轭物具有许多优点。本文还描述了制备和使用这些共轭物的方法。
• Multifunctional stealth nanoparticles for biomedical use
  申请人：Centre National de la Recherche Scientifique

  公开号：EP2210616A1

  公开（公告）日：2010-07-28

  The present invention relates to the field of drug delivery nanosystems. More precisely, the present invention concerns a copolymer with advantageous properties for the outer coating of various nanoparticles. Said copolymer comprises at least three types of monomers with stealthy, coupling and therapeutic properties respectively, as well as an optional fourth type of monomers with targeting properties. The present invention also relates to core-shell or hollow shell nanoparticles coated by an external layer of the copolymer according to the invention. Several types of core-shell nanoparticles are envisaged. The invention also concerns methods for preparing said nanoparticles, as well as pharmaceutical compositions or medicaments comprising them.

  本发明涉及给药纳米系统领域。更确切地说，本发明涉及一种具有优势特性的共聚物，可用于各种纳米粒子的外涂层。所述共聚物包括至少三种分别具有隐形、耦合和治疗特性的单体，以及可选的第四种具有靶向特性的单体。本发明还涉及由本发明共聚物外层包覆的核壳或空壳纳米粒子。本发明设想了多种类型的核壳纳米粒子。本发明还涉及制备上述纳米粒子的方法，以及包含这些纳米粒子的药物组合物或药物。
• Coiled Coil Peptides as Universal Linkers for the Attachment of Recombinant Proteins to Polymer Therapeutics
  作者：Michal Pechar、Robert Pola、Richard Laga、Karel Ulbrich、Lucie Bednárová、Petr Maloň、Irena Sieglová、Vlastimil Král、Milan Fábry、Ondřej Vaněk

  DOI：10.1021/bm200897b

  日期：2011.10.10

  We have designed, synthesized, and characterized peptides containing four repeats of the sequences VAALEKE (peptide E) or VAALKEK (peptide K). While the peptides alone adopt in aqueous solutions a random coil conformation, their equimolar mixture forms heterodimeric coiled coils as confirmed by CD spectroscopy. S-Azidopentanoic acid was connected to the N-terminus of peptide E via a short poly(ethylene glycol) spacer. The terminal azide group enabled conjugation of the peitide with a synthetic drug carrier based on the N-(2-hydrokypropyl)methacrylamide copolymer containing propargyl groups using "click" chemistry. When incorporated into the polymer drug carrier, peptide E formed a stable noncovalent complex with peptide K beloning to a recombinant single-chain fraginent (scFv) of the M75 antibody. The complex thereby mediates a noncovalent linkage between the polymer drug carrier and the protein. The recombinant scFv antibody fragment was selected as a targeting ligand against carbonic anhydrase IX-a marker overexpressed by tumor cells of various human carcinomas. The antigen binding affinity of the polymer-scFv complex was confirmed by ELISA. This approach offers a well-defined, specific, and nondestructive universal method for the preparation of protein (antibody)-targeted polymer drug and gene carriers designed for cell-specific delivery.