甲氨蝶呤与聚酰胺-胺（PAMAM）树枝状大分子平台的无铜点击共轭。
Copper-free click conjugation of methotrexate to a PAMAM dendrimer platform.
作者信息
Huang Baohua, Desai Ankur, Zong Hong, Tang Shengzhuang, Leroueil Pascale, Baker James R
机构信息
Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, Ann Arbor, Michigan 48109, USA.
出版信息
Tetrahedron Lett. 2011 Mar 30;52(13):1411-1414. doi: 10.1016/j.tetlet.2010.12.025.
Abstract
The synthesis of a generation 5 (G5) poly(amidoamine) (PAMAM) dendrimer platform having cyclooctyne ligands that were subsequently be used for a copper-free Huisgen 1,3-dipolar cycloaddition (click reaction) with azido modified methotrexate is described. The G5 PAMAM dendrimer was first partially (70%) acetylated and then coupled with 20 cyclooctyne ligands through amide bonds. The remaining primary amine groups on the dendrimer surface were neutralized by acetylation. The platform was then "clicked" with different numbers (5, 10, and 17) of γ-azido functionalized methotrexate. The copper-free click reactions were stoichiometric with excellent yields.
摘要
描述了具有环辛炔配体的第5代（G5）聚（酰胺胺）（PAMAM）树枝状大分子平台的合成，该平台随后用于与叠氮基修饰的甲氨蝶呤进行无铜的惠斯根1,3-偶极环加成反应（点击反应）。首先将G5 PAMAM树枝状大分子部分（70%）乙酰化，然后通过酰胺键与20个环辛炔配体偶联。树枝状大分子表面剩余的伯胺基团通过乙酰化中和。然后将该平台与不同数量（5、10和17）的γ-叠氮基功能化甲氨蝶呤进行“点击”反应。无铜点击反应是化学计量的，产率优异。
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本文引用的文献
1
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J Am Chem Soc. 2010 Aug 25;132(33):11799-805. doi: 10.1021/ja105005t.
2
Copper-free click chemistry for highly luminescent quantum dot conjugates: application to in vivo metabolic imaging.无铜点击化学用于高发光量子点偶联物：在体内代谢成像中的应用。
Bioconjug Chem. 2010 Apr 21;21(4):583-8. doi: 10.1021/bc900564w.
3
The synthesis of a c(RGDyK) targeted SN38 prodrug with an indolequinone structure for bioreductive drug release.合成具有吲哚醌结构的靶向 c(RGDyK)的 SN38 前药用于还原型药物释放。
Org Lett. 2010 Apr 2;12(7):1384-7. doi: 10.1021/ol1002626.
4
Strain-promoted alkyne azide cycloaddition for the functionalization of poly(amide)-based dendrons and dendrimers.应变促进的炔叠氮环加成反应在聚酰胺基树枝状分子和树枝状聚合物的功能化中的应用。
J Am Chem Soc. 2010 Mar 24;132(11):3923-31. doi: 10.1021/ja910581d.
5
A quantitative assessment of nanoparticle-ligand distributions: implications for targeted drug and imaging delivery in dendrimer conjugates.纳米粒子-配体分布的定量评估：对树枝状聚合物缀合物中靶向药物和成像传递的影响。
ACS Nano. 2010 Feb 23;4(2):657-70. doi: 10.1021/nn900999c.
6
Targeting the efficacy of a dendrimer-based nanotherapeutic in heterogeneous xenograft tumors in vivo.针对基于树枝状高分子的纳米治疗剂在异种移植肿瘤体内的疗效。
Anticancer Drugs. 2010 Feb;21(2):186-92. doi: 10.1097/CAD.0b013e328334560f.
7
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Bioconjug Chem. 2009 Nov;20(11):2001-16. doi: 10.1021/bc900087a.
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Cu-catalyzed azide-alkyne cycloaddition.铜催化的叠氮化物-炔烃环加成反应
Chem Rev. 2008 Aug;108(8):2952-3015. doi: 10.1021/cr0783479.
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Biomacromolecules. 2008 Feb;9(2):603-9. doi: 10.1021/bm701185p. Epub 2008 Jan 15.
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