PREFERENTIAL BINDING OF CARBOXYLATE FORM OF CAMTOTHECIN BY HUMAN SERUM ALBUMIN

喜树碱显示出前所未有的抗肿瘤活性 人类结肠癌。到目前为止，它的全部治疗作用是 受限于较差的水溶性和水溶液的不稳定性 内酯环部分。开环速度快，形成完整的 丧失生物活性。在已发布的报告中，我们展示了 脂质体结合的喜树碱是稳定的，因此表明 脂质体可以作为有用的药物输送系统用于增溶 喜树碱及其内酯环和抗肿瘤的保存 活动。为了研究分子的平衡关联 喜树碱与脂质双层，我们利用了药物的强烈 本征荧光。荧光与扩展的 喹啉环系的共轭。基于与Small的关联 L-`-二肉豆蔻酰基组成的单层囊泡 喜树碱的磷脂酰甘油(DMPG)发射光谱 发射光谱向更低的波长移动，或蓝移，约16% NM。这些光谱位移允许测量结合常数。

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.