N2-(4-(((2-amino-4-hydroxypteridin-6-yl)methyl)amino)benzoyl)-N5-(2-azidoethyl)-L-glutamine | 1498411-23-6

• 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
• 英文名称: N2-(4-(((2-amino-4-hydroxypteridin-6-yl)methyl)amino)benzoyl)-N5-(2-azidoethyl)-L-glutamine
• CAS: 1498411-23-6
• 化学式: C₂₁H₂₃N₁₁O₅
• 分子量: 509.484
• InChiKey: MWSAKNZIAVNPLH-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  37.0
• 可旋转键数：
  12.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  253.84
• 氢给体数：
  6.0
• 氢受体数：
  10.0

反应信息

• 作为产物：
  描述：

  folate 、 2-叠氮基乙胺 在 N-羟基丁二酰亚胺 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 37.0h， 以70%的产率得到N2-(4-(((2-amino-4-hydroxypteridin-6-yl)methyl)amino)benzoyl)-N5-(2-azidoethyl)-L-glutamine
  参考文献：
  名称：

  用于多功能细胞内药物递送的靶向可点击和肿瘤可裂解的聚氨酯纳米肽的构建

  摘要：

  癌症治疗迫切需要构建多功能纳米车辆的新策略，以克服靶向递送的多重挑战。为了满足这些需求，我们开发了一种新型的靶向可点击和可肿瘤裂解的聚氨酯纳米胶束，用于多功能递送抗肿瘤药物。聚氨酯是由生物可降解的聚（ε -己内酯）（PCL）和合成升赖氨酸乙酯二异氰酸酯（LDI），通过一个新的设计的进一步扩展升-胱氨酸衍生化的扩链剂，带有氧化还原响应性二硫键和可点击的炔基（Cys-PA），最后被具有高度pH敏感的苯甲亚胺键（BPEG）的可分离甲氧基-聚（乙二醇）终止。所获得的聚合物显示出有吸引力的自组装特性和刺激响应性，良好的细胞相容性以及对阿霉素（DOX）的高负载能力。此外，叶酸（FA）作为模型靶向配体通过有效的点击反应与聚氨酯胶束结合。FA的修饰导致体外对FA受体阳性HeLa癌细胞的细胞摄取增强，药物作用增强。作为概念证明，

  DOI：

  10.1021/bm401342t

文献信息

• Targeted delivery and enhanced gene-silencing activity of centrally modified folic acid–siRNA conjugates
  作者：Lidya Salim、Golam Islam、Jean-Paul Desaulniers

  DOI：10.1093/nar/gkz1115

  日期：2020.1.10

  One of the major hurdles in RNAi research has been the development of safe and effective delivery systems for siRNAs. Although various chemical modifications have been proposed to improve their pharmacokinetic behaviour, their delivery to target cells and tissues presents many challenges. In this work, we implemented a receptor-targeting strategy to selectively deliver siRNAs to cancer cells using folic acid as a ligand. Folic acid is capable of binding to cell-surface folate receptors with high affinity. These receptors have become important molecular targets for cancer research as they are overexpressed in numerous cancers despite being expressed at low levels in normal tissues. Employing a post-column copper-catalyzed alkyne–azide cycloaddition (CuAAC), we report the synthesis of siRNAs bearing folic acid modifications at different positions within the sense strand. In the absence of a transfection carrier, these siRNAs were selectively taken up by cancer cells expressing folate receptors. We show that centrally modified folic acid–siRNAs display enhanced gene-silencing activity against an exogenous gene target (∼80% knockdown after 0.75 μM treatment) and low cytotoxicity. In addition, these siRNAs achieved potent dose-dependent knockdown of endogenous Bcl-2, an important anti-apoptotic gene.

  摘要：RNAi研究中的一个主要障碍是开发安全有效的siRNA传递系统。尽管提出了各种化学修饰以改善它们的药代动力学行为，但将其传递到靶细胞和组织面临许多挑战。在这项工作中，我们实施了一种受体靶向策略，利用叶酸作为配体选择性地将siRNA传递到癌细胞中。叶酸能够与细胞表面的叶酸受体高亲和结合。这些受体已成为癌症研究的重要分子靶标，因为它们在许多癌症中过度表达，尽管在正常组织中表达水平较低。通过使用柱后铜催化的炔-叠氮環加成（CuAAC），我们报道了在感应链上不同位置带有叶酸修饰的siRNA的合成。在没有转染载体的情况下，这些siRNA被表达叶酸受体的癌细胞选择性地摄取。我们展示，中心修饰的叶酸-siRNA对外源基因靶（在0.75 μM处理后约80%的沉默）显示出增强的基因沉默活性和低细胞毒性。此外，这些siRNA对内源性Bcl-2的有效剂量依赖性沉默取得了显著的效果，Bcl-2是一个重要的抗凋亡基因。
• Dual functionalized telechelic block copolymers with reproducible block sizes prepared by microwave assisted RAFT polymerization
  作者：Kaushik Mishra、Abraham Joy

  DOI：10.1016/j.polymer.2015.04.013

  日期：2015.6

  This work demonstrates the preparation of amphiphilic block copolymers with remarkable reproducibility of each block and the dual functionalization of the chain ends with a targeting unit and a fluorescent moiety. The size of the resulting micelles can be controlled between 17 and 55 nm by tuning the size of the hydrophobic block. The polymerization of the diblock was carried out by microwave assisted reversible addition fragmentation chain transfer (RAFT) polymerization and results in a very high degree of reproducibility of the number of repeat units of each block. The hydrophilic block of the polymer comprised of poly(2-hydroxyethyl acrylate) (pHEA) while the hydrophobic block was made of poly(2-ethylhexyl acrylate) (pEHA). Folic acid, a folate receptor targeting moiety, was tethered to the alpha end of the polymer while anthracene was covalently linked to the omega end. The omega end covalent attachment is via a redox cleavable disulfide bond, which is optimal for controlled drug delivery systems. High efficiencies of alpha- and omega-conjugations were obtained as determined by UV and NMR measurements. (C) 2015 Elsevier Ltd. All rights reserved.