N-(N-(N-(N-methacryloylglycyl)phenylalanyl)leucyl)glycine p-nitrophenyl ester

• 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: N-(N-(N-(N-methacryloylglycyl)phenylalanyl)leucyl)glycine p-nitrophenyl ester
• 英文别名: (N-methacryloylglycyl)-L-phenylalanyl-l-leucylglycine 4-nitrophenyl ester；N-methacryloyl-glycyl-L-phenylalanyl-L-leucylglycine p-nitrophenyl ester；N-methacryloylglycyl-L-phenylalanyl-L-leucylglycine 4-nitrophenyl ester；N-methacryloyl-glycylphenylalanylleucylglycine p-nitrophenyl ester；N-methacryloylglycylphenylalanylleucylglycine 4-nitrophenyl ester；N-methacroylglycylphenylalanylleucylglycine p-nitrophenyl ester；(4-nitrophenyl) 2-[[(2S)-4-methyl-2-[[(2S)-2-[[2-(2-methylprop-2-enoylamino)acetyl]amino]-3-phenylpropanoyl]amino]pentanoyl]amino]acetate
• 化学式: C₂₉H₃₅N₅O₈
• 分子量: 581.626
• InChiKey: XAPVMQZOUOJMRM-ZEQRLZLVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  42
• 可旋转键数：
  15
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  189
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  盐酸多柔比星 、 N-(N-(N-(N-methacryloylglycyl)phenylalanyl)leucyl)glycine p-nitrophenyl ester 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (N-methacryloylglycyl)-L-phenylalanylleucylglycyldoxorubicin
  参考文献：
  名称：

  骨架可降解多嵌段 N-(2-羟丙基) 甲基丙烯酰胺共聚物通过可逆加成-断裂链转移聚合和硫醇-烯偶联反应共轭

  摘要：

  遥爪水溶性 HPMA 共聚物和 HPMA 共聚物-多柔比星 (DOX) 共轭物已通过 RAFT 聚合合成，该聚合由含有酶促降解寡肽序列的新型双功能链转移剂 (CTA) 介导。后聚合氨解，然后用双马来酰亚胺进行链扩展，产生线性高分子量多嵌段 HPMA 共聚物缀合物。这些聚合物是可酶降解的；除了释放药物 (DOX) 外，聚合物骨架的降解导致产物的分子量与起始材料相似且低于肾阈值。新的多嵌段 HPMA 共聚物具有作为抗癌药物新载体的潜力。

  DOI：

  10.1021/bm101254e

文献信息

• Novel star HPMA-based polymer conjugates for passive targeting to solid tumors
  作者：T. Etrych、J. Strohalm、P. Chytil、B. Říhová、K. Ulbrich

  DOI：10.3109/1061186x.2011.622402

  日期：2011.12

  molecule formed by poly(amido amine) (PAMAM) dendrimers was grafted with semitelechelic N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers bearing doxorubicin (Dox) attached by hydrazone bonds enabling intracellular pH-controlled hydrolytic drug release, or by GFLG sequence susceptible to enzymatic degradation. The controlled synthesis utilizing semitelechelic copolymer precursors facilitated preparation

  已经开发出了设计用于被动肿瘤靶向的新型星形聚合物-阿霉素结合物，并且已经研究了其治疗癌症的潜力。在本研究中，描述了缀合物的合成，理化特性，药物释放，生物分布以及体内功效的初步数据。在水溶性共轭物中，由聚酰胺胺（PAMAM）树状大分子形成的分子的核心接枝有半telechelic N带有阿霉素（Dox）的（2-羟丙基）甲基丙烯酰胺（HPMA）共聚物通过hydr键连接，从而使细胞内pH控制水解药物释放，或通过易酶解的GFLG序列。利用半遥望共聚物前体进行的受控合成促进了分子量范围广（1.1–3.0·10 5 g / mol）的聚合物共轭物的制备。与游离药物或线性缀合物相反，星形聚合物-Dox缀合物在荷瘤小鼠中表现出延长的血液循环和增强的肿瘤蓄积，表明EPR作用的重要作用。星形聚合物-Dox共轭物在体内显示出明显更高的抗肿瘤活性如果以单剂量15或5 mg Dox eq./kg处理，则比Dox·HC
• Amplification of biotin-mediated targeting
  申请人：Russell-Jones Gregory

  公开号：US20060127310A1

  公开（公告）日：2006-06-15

  The present invention relates to the delivery of drug, peptide and protein pharmaceuticals using a biotin-mediated uptake system. More particularly the invention relates to the amplification of active substance delivery with the biotin uptake system using a biotin-active substance-polymer conjugate or a biotin-nanoparticle conjugate. The invention also relates to processes for preparing the conjugates, pharmaceutical and diagnostic compositions containing same and methods of diagnosis and treatment involving the conjugates.

  本发明涉及使用生物素介导的摄取系统传递药物、肽和蛋白质药物。更具体地，本发明涉及使用生物素-活性物质-聚合物共轭物或生物素-纳米粒子共轭物增强生物素摄取系统的活性物质传递。本发明还涉及制备这些共轭物的过程，包含它们的制药和诊断组合物以及涉及这些共轭物的诊断和治疗方法。
• Gold/lanthanide nanoparticle conjugates and uses thereof
  申请人：COLORADO SCHOOL OF MINES

  公开号：US10406111B2

  公开（公告）日：2019-09-10

  The present disclosure is directed generally to gold/lanthanide nanoparticle conjugates, such as gold/gadolinium nanoparticle conjugates, nanoparticle conjugates including polymers, nanoparticle conjugates conjugated to targeting agents and therapeutic agents, and their use in targeting, treating, and/or imaging disease states in a patient.

  本公开总体上针对金/镧系元素纳米粒子共轭物，如金/钆纳米粒子共轭物、包括聚合物在内的纳米粒子共轭物、与靶向药物和治疗药物共轭的纳米粒子共轭物，以及它们在靶向、治疗和/或成像患者疾病状态中的用途。
• DRUG DELIVERY SYSTEM FOR THE SIMULTANEOUS DELIVERY OF DRUGS ACTIVATABLE BY ENZYMES AND LIGHT
  申请人：UNIVERSITY OF UTAH

  公开号：EP0621880B1

  公开（公告）日：1999-09-08
• ——
  作者：Yuji Kasuya、Zheng‐Rong Lu、Pavla Kopečková、S. Esmail Tabibi、Jindřich Kopeček

  DOI：10.1023/a:1014216712820

  日期：——

  Purpose. To optimize the structure of geldanamycin (GDM) derivative moieties attached to N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers via an enzymatically degradable spacer.Methods HPMA copolymers containing different AR-GDM (AR=3-aminopropyl (AP), 6-aminohexyl (AH), and 3-amino-2-hydroxypropyl AP(OH)) were synthesized and characterized. Their cytotoxicity towards the A2780 human ovarian carcinoma cells was evaluated.Results The cytotoxic efficacy of HPMA copolymer-AR-GDM conjugates depended on the structure of AR-GDM. Particularly, HPMA copolymer-bound AH-GDM, which possessed the longest substituent at the 17-position, demonstrated the highest efficacy among the polymer-bound GDM derivatives; however the activity of free AH-GDM was lower than that of the other free AR-GDMs. The relative increase of the activity of macromolecular AH-GDM when compared to AP-GDM or AP(OH)-GDM correlated with the enhanced recognition of AH-GDM terminated oligopeptide side-chains by the active site of the lysosomal enzyme, cathepsin B. Drug stability and further stabilization upon binding to HPMA copolymer also contributed to the observed phenomena.Conclusions AH-GDM was found to be a suitable GDM derivative for the design of a drug delivery system based on HPMA copolymers and enzymatically-degradable spacers.