• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法,用中文像聊天一样搜索,搜遍4000万医学文献。AI智能推荐,让科研检索更轻松。

立即免费搜索

文件翻译

保留排版,准确专业,支持PDF/Word/PPT等文件格式,支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述,25分钟生成高质量综述,智能提取关键信息,辅助科研写作。

立即免费体验

Improvement of hepatocyte-specific gene expression by a targeted colchicine prodrug.

作者信息

van Rossenberg Sabine M W, Sliedregt-Bol Karen M, Koning Gerben, van den Elst Hans, van Berkel Theo J C, van Boom Jacques H, van der Marel Gijs A, Biessen Erik A L

机构信息

Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.

出版信息

Chembiochem. 2003 Jul 7;4(7):633-9. doi: 10.1002/cbic.200300582.

DOI:10.1002/cbic.200300582
PMID:12851933
Abstract

Colchicine, an established tubulin inhibitor, interferes with the trafficking of endocytotic vesicles and thereby promotes the escape of lysosome-entrapped compounds. To improve its potency and cell specificity, a targeted prodrug of colchicine was synthesized by conjugation to a high-affinity ligand (di-N(alpha),N(epsilon)-(5-(2-acetamido-2-deoxy-beta-D-galactopyranosyloxy)pentanomido)lysine, K(GalNAc)(2)) for the asialoglycoprotein receptor on parenchymal liver cells. The resulting colchicine-K(GalNAc)(2) conjugate bound to this receptor with an affinity of 4.5 nM. Confocal microscopy studies confirmed rapid uptake and receptor dependency of a prodrug conjugated with fluorescein isothiocyanate. Colchicine-K(GalNAc)(2) substantially increased the transfection efficiency of polyplexed DNA in parenchymal liver cells in a concentration- and receptor-dependent fashion. Colchicine-K(GalNAc)(2) was found to enhance the transfection efficiency by 50-fold at 1 nM, whereas the parental colchicine was ineffective. In conclusion, this nontoxic colchicine-K(GalNAc)(2) conjugate can be a useful tool to improve the transfection efficiency of hepatic nonviral gene transfer vehicles.

摘要

相似文献

1
Improvement of hepatocyte-specific gene expression by a targeted colchicine prodrug.
Chembiochem. 2003 Jul 7;4(7):633-9. doi: 10.1002/cbic.200300582.
2
Targeted delivery of oligodeoxynucleotides to parenchymal liver cells in vivo.体内将寡脱氧核苷酸靶向递送至肝实质细胞。
Biochem J. 1999 Jun 15;340 ( Pt 3)(Pt 3):783-92.
3
A targeted peptide nucleic acid to down-regulate mouse microsomal triglyceride transfer protein expression in hepatocytes.一种靶向肽核酸,用于下调肝细胞中小鼠微粒体甘油三酯转移蛋白的表达。
Bioconjug Chem. 2003 Nov-Dec;14(6):1077-82. doi: 10.1021/bc0340417.
4
A hepatocyte-targeted conjugate capable of delivering biologically active colchicine in vitro.一种能够在体外递送具有生物活性秋水仙碱的肝细胞靶向共轭物。
Bioconjug Chem. 1996 Jan-Feb;7(1):131-7. doi: 10.1021/bc950083m.
5
Mechanisms of co-modified liver-targeting liposomes as gene delivery carriers based on cellular uptake and antigens inhibition effect.基于细胞摄取和抗原抑制作用的共修饰肝靶向脂质体作为基因递送载体的机制
J Control Release. 2007 Feb 12;117(2):281-90. doi: 10.1016/j.jconrel.2006.11.006. Epub 2006 Nov 16.
6
Design of a targeted peptide nucleic acid prodrug to inhibit hepatic human microsomal triglyceride transfer protein expression in hepatocytes.一种靶向肽核酸前药的设计,用于抑制肝细胞中肝人微粒体甘油三酯转移蛋白的表达。
Bioconjug Chem. 2002 Mar-Apr;13(2):295-302. doi: 10.1021/bc015550g.
7
Targeted lysosome disruptive elements for improvement of parenchymal liver cell-specific gene delivery.用于改善实质肝细胞特异性基因递送的靶向溶酶体破坏元件。
J Biol Chem. 2002 Nov 29;277(48):45803-10. doi: 10.1074/jbc.M203510200. Epub 2002 Sep 16.
8
Enhanced hepatocyte-selective in vivo gene expression by stabilized galactosylated liposome/plasmid DNA complex using sodium chloride for complex formation.使用氯化钠形成复合物的稳定化半乳糖基化脂质体/质粒DNA复合物增强体内肝细胞选择性基因表达。
Mol Ther. 2004 Oct;10(4):719-29. doi: 10.1016/j.ymthe.2004.07.015.
9
N-Acetylgalactosamine Block-co-Polycations Form Stable Polyplexes with Plasmids and Promote Liver-Targeted Delivery.N-乙酰半乳糖胺嵌段共聚物与质粒形成稳定的多聚体并促进肝脏靶向递送。
Biomacromolecules. 2016 Mar 14;17(3):830-40. doi: 10.1021/acs.biomac.5b01555. Epub 2016 Feb 8.
10
Conjugation of mono and di-GalNAc sugars enhances the potency of antisense oligonucleotides via ASGR mediated delivery to hepatocytes.单糖和双糖N-乙酰半乳糖胺的缀合通过ASGR介导的向肝细胞递送增强了反义寡核苷酸的效力。
Bioorg Med Chem Lett. 2016 Aug 1;26(15):3690-3. doi: 10.1016/j.bmcl.2016.05.084. Epub 2016 May 28.