PREFERENTIAL BINDING OF CARBOXYLATE FORM OF CAMTOTHECIN BY HUMAN SERUM ALBUMIN

喜树碱羧酸盐形式与人血清白蛋白的优先结合

• 批准号: 6282888
• 负责人: THOMAS G BURKE
• 金额: $ 2.55万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6282888
• 关键词: biological products; biomedical equipment development; biomedical resource; human tissue; informatics; spectrometry

Camptothecin displays unprecedented antitumor activities against human colon cancer. To date its full therapeutic utility has been limited by poor water-solubility and the aqueous instability of the lactone ring moiety. Ring opening is rapid, resulting in a complete loss of biological activity. In published reports, we demonstrate that liposome-bound camptothecin is stable, thus suggesting that liposomes may serve as useful drug delivery systems for solubilizing camptothecin and preserving both its lactone ring and antitumor activity. In order to study the equilibrium association of camptothecin with lipid bilayers, we exploited the drug's intense intrinsic fluorescence. Fluorescence is associated with the extended conjugation of the quinoline ring system. Upon association with small unilamellar vesicles (SUVs) composed of L-`-dimyristoyl phosphatidylglycerol (DMPG), the emission spectra of camptothecin's emission spectrum shifts to lower wavelength, or blue shifts, some 16 nm. These spectral shifts allow the binding constants to be measured.

喜树碱显示出前所未有的抗肿瘤活性， 人类结肠癌 迄今为止，其全部治疗效用已被 由于水溶性差和水不稳定性的限制， 内酯环部分。 开环是迅速的，导致一个完整的 丧失生物活性。 在已发表的报告中，我们证明 脂质体结合的喜树碱是稳定的，因此表明， 脂质体可以用作用于溶解 喜树碱及其内酯环保留和抗肿瘤作用 活动 为了研究植物的平衡结合， 喜树碱与脂质双层，我们利用药物的强烈 内源荧光 荧光与扩展的 喹啉环系统的共轭。 在与小 由L-`-二肉豆蔻酰组成的单层囊泡（SUV 磷脂酰甘油（DMPG），喜树碱的发射光谱 发射光谱向较低波长移动，或蓝移，约16 nm. 这些光谱位移允许测量结合常数。