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新型分子药物载体:奥沙利铂在葫芦[7]脲中的包封及其对药物稳定性和反应活性的影响。

Novel molecular drug carrier: encapsulation of oxaliplatin in cucurbit[7]uril and its effects on stability and reactivity of the drug.

作者信息

Jeon Young Jin, Kim Soo-Young, Ko Young Ho, Sakamoto Shigeru, Yamaguchi Kentaro, Kim Kimoon

机构信息

National Creative Research Initiative Center for Smart Supramolecules, Division of Molecular and Life Sciences, Pohang University of Science and Technology San 31 Hyojadong, Pohang 790-784, Republic of Korea.

出版信息

Org Biomol Chem. 2005 Jun 7;3(11):2122-5. doi: 10.1039/b504487a. Epub 2005 Apr 28.

Abstract

Oxaliplatin forms a stable 1:1 inclusion complex with cucurbit[7]uril as indicated by NMR, mass spectrometry, isothermal titration calorimetry and X-ray crystallography. The encapsulation of the drug results in a large enhancement in stability, a moderate decrease in reactivity toward guanosine but a much larger decrease in reactivity toward L-methionine, which suggests the encapsulation not only increases the stability of the drug but also may reduce unwanted side effects caused by protein binding of the platinum drug. A preliminary in vitro assay using various tumor cell lines reveals that the encapsulation results in a decrease in the antitumor activity of oxaliplatin.

摘要

核磁共振、质谱、等温滴定量热法和X射线晶体学表明,奥沙利铂与葫芦[7]脲形成稳定的1:1包合物。药物的包封导致稳定性大幅提高,对鸟苷的反应性适度降低,但对L-甲硫氨酸的反应性降低幅度更大,这表明包封不仅增加了药物的稳定性,还可能减少铂类药物与蛋白质结合引起的不良副作用。使用各种肿瘤细胞系进行的初步体外试验表明,包封导致奥沙利铂的抗肿瘤活性降低。

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