来自oxanorbornadiene试剂的可降解合物
Alexander A Kislukhin1, Cody J Higginson, Vu P Hong
1Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Journal of the American Chemical Society
|March 30, 2012
概括
氧化纳米二烯碳酸盐 (OND) 试剂使得从血清白蛋白载体中控制药物释放. 通过修改OND链接,药物释放率可以从几分钟调整为几天,以实现多功能治疗应用.
科学领域:
- 化学生物学 化学生物学
- 药物运输 药物运输 药物运输
- 生物结合化学 生物结合化学
背景情况:
- 血清白蛋白是药物输送的关键宏分子载体.
- 开发高效可控的药物释放机制对于治疗疗效至关重要.
研究的目的:
- 探索oxanorbornadienedicarboxylate (OND) 试剂,用于从血清白蛋白中结合和释放药物.
- 调查影响 adduct 稳定性和药物释放动态的修改.
主要方法:
- 合成和表征30多个模型的OND添加物与硫醇和氨基.
- 反应动力学研究涉及牛血清白蛋白 (BSA) 囊和氨基残留物.
- 在各种条件下 (pH,温度) 评估OND-adduct的稳定性.
- 使用光货物的药物释放概况的评估.
主要成果:
- 在中微分子度下,OND试剂在几分钟内有效标记BSA氨酸残留物.
- 在模型系统中观察到醇高选择性 (>1000倍) 超过氨基标签,但蛋白质氨基标签也很实用.
- 与OND-胺添加物相比,OND-胺添加物具有高达15倍的稳定性,并且对酸催化释放敏感.
- BSA的药物释放半衰期从40分钟到7天不等,可以通过OND链接修改进行调整.
结论:
- OND试剂为从蛋白质载体中开发可调节的药物释放系统提供了一个多功能平台.
- 通过修改OND链接来控制释放率的能力为药物输送应用提供了宝贵的工具.
相关概念视频
00:53Olefin Metathesis Polymerization: Acyclic Diene Metathesis (ADMET)
Acyclic diene metathesis polymerization or ADMET polymerization involves cross-metathesis of terminal dienes, such as 1,8-nonadiene, to give linear unsaturated polymer and ethylene. As ADMET is a reversible process, the formed ethylene gas must be removed from the reaction mixture to complete the polymerization process.
Similar to cross-metathesis, ADMET also involves the formation of metallacyclobutane intermediate by [2+2] cycloaddition of one of the double bonds of a terminal diene with...
Similar to cross-metathesis, ADMET also involves the formation of metallacyclobutane intermediate by [2+2] cycloaddition of one of the double bonds of a terminal diene with...
03:08Hydroboration-Oxidation of Alkenes
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02:47Alkynes to Aldehydes and Ketones: Hydroboration-Oxidation
Introduction
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02:04Oxidation of Alkenes: Anti Dihydroxylation with Peroxy Acids
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02:36Regioselectivity and Stereochemistry of Hydroboration
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Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.