聚乙二醇氨基酸衍生物的合成及其对紫杉醇的修饰

Modification of Taxol with amino acids derivatives of polyethylene glycol

摘要: 为获得可溶性聚乙二醇(PEG)化紫杉醇，制备了不同相对分子质量的PEG氨基酸衍生物，并通过氨基酸连接臂将PEG连接到紫杉醇上，获得了具有特殊连接臂的PEG化紫杉醇。PEG化紫杉醇水溶性较天然紫杉醇提高了约1 000倍，且对MCF-7和SGC-7901等肿瘤细胞都具有显著抑制作用，并呈现出明显的浓度依赖性。研究结果显示：PEG氨基酸衍生物对紫杉醇的化学修饰能够显著提高紫杉醇的水溶性，并保留其体外抗肿瘤活性，此类PEG氨基酸衍生物可以用于设计具有特殊连接臂的紫杉醇前药。

Abstract: Water-soluble Taxol prodrugs were prepared by attaching Taxol to PEG chain with different molecular weight through different amino acid spacers.The water-solubility of PEGylated Taxol increased more than 1 000 times compared with Taxol.In vitro antitumor test of PEGylated Taxol against MCF-7 and SGC-7901 cell lines showed good antitumor activity in a concentration-dependent manner.The water-solubility of Taxol was improved significantly by modification with amino acid derivatives of polyethylene glycol while in vitro antitumor activity was retained,which was the main purpose of chemical modification of Taxol.