E-选择素肽配体及其与羟基喜树碱的偶联物合成与抗肿瘤活性评价

Synthesis and Antitumor Evaluation of E-Selectin Peptide Ligand and its Conjugates with 10-Hydroxyl Camptothecin

利用固相合成方法设计并合成了12个E–选择素七肽配体(IELLQAR)的衍生肽分子(1—12)以及3个肽分子配体(1)与羟基喜树碱的偶联物(13—15).体外肿瘤细胞HL-60与血管内皮细胞HUVEC的黏附实验表明:在1μmol/L测试浓度下,多个肽分子(1、7、8、10、11、12)表现出比已报道七肽(2)更好的活性.进一步的评价显示偶联物基本保留了原药HCPT的细胞毒活性,同时具备肽配体的抗黏附活性,而多肽分子本身并没有明显的细胞毒作用.尤其偶联物13和14在0.3μmol/L浓度下有显著的抗黏附作用,说明偶联物在同样浓度水平下可同时发挥抗肿瘤和抗黏附作用.上述结果表明该类肽分子具有应用于肿瘤靶向和抗肿瘤转移的潜力.

Based on a reported E-selectin peptide ligand(IELLQAR),12 modified peptide molecules(1-12)three conjugates of hydroxycamptothecin and peptide 1(13-15)were obtained through solid-phase synthesis.The anti-adhesion experiment of tumor cells(HL-60)and endothelial cells(HUVEC)in vitro showed that several peptides(1,7,8,10,11 and 12)exhibited better activities than IELLQAR(2)with 1μmol/L.The cytotoxicity test indicated that the conjugates retained the anticancer activity of HCPT,while the peptide molecule itself had no obvious cytotoxicity.The anti-adhesion test in vitro showed that the anti-adhesion effect of conjugate 13 and 14 was retained even under the concentration of 0.3μmol/L.These results suggested that this kind of peptide molecule has potential for tumor targeting and anti-tumor metastasis.