Luan Yepeng, Jing Fanbo, Zhang Jian, Zou Mingming, Wang Xuejian, Jia Yuping, Liu Ning, Mou Jiajia, Xu Wenfang
Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, Shandong, 250012, China.
Protein Pept Lett. 2012 Oct;19(10):1122-31. doi: 10.2174/092986612802762615.
Aminopeptidase N (APN/CD13) of the M1 family is a broad specificity enzyme that is intimately involved in tumor angiogenesis and metastasis. Asparagine-glycine-arginine (NGR) is a tumor-homing tripeptide, which can selectively combine with APN/CD13 that is overexpressed on the surface of some tumor cells. Various anti-tumor drugs can be conjugated to NGR to improve selectivity, efficacy, and to decrease drug toxicity. In this study, a tripeptide NGR(NO2) was synthesized and conjugated with 5-fluorouracil. The anti-tumor activities of this new prodrug were evaluated in vivo. More significant anti-tumor effects were observed over the parent 5-fluorouracil.
M1家族的氨肽酶N（APN/CD13）是一种具有广泛特异性的酶，它与肿瘤血管生成和转移密切相关。天冬酰胺-甘氨酸-精氨酸（NGR）是一种肿瘤归巢三肽，它可以选择性地与某些肿瘤细胞表面过度表达的APN/CD13结合。各种抗肿瘤药物可以与NGR偶联，以提高选择性、疗效并降低药物毒性。在本研究中，合成了三肽NGR(NO2)并将其与5-氟尿嘧啶偶联。在体内评估了这种新前药的抗肿瘤活性。观察到其抗肿瘤效果比母体5-氟尿嘧啶更显著。
