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以N-芴甲氧羰基-L-亮氨酸(Fmoc-Leu-OH)和N-芴甲氧羰基脯氨酸(Fmoc-Pro-OH)为原料,采用经典的Fmoc固相合成法,通过对氨基酸N端的保护及脱保护、氨基酸的甲基化、缩合等步骤合成线性五肽,以缩合试剂六氟磷酸苯并三唑-1-基氧基三吡咯烷基磷(Py BOP)关环,分别以59.5%和41.1%的环合收率得到了两个新的环五肽化合物G_1和G_2,结构通过~1HNMR、~(13)CNMR、ESI-MS进行确认。采用MTT法对目标化合物G_1和G_2进行了体外抗肿瘤活性的研究。结果表明:含有脯氨酸片段的Galaxamide类似物G_2具有良好的活性,尤其对人乳腺癌细胞株(MCF-7)具有较好的细胞毒性,其IC_(50)值为5.85 mg/L。
Fmoc-Leu-OH and N-fluorenylmethoxycarbonyl proline (Fmoc-Pro-OH) were used as raw materials, and by the classical Fmoc solid phase synthesis method, The protection and deprotection of the N-terminal amino acid, the methylation of the amino acid, the condensation and other steps were used to synthesize the linear pentapeptide and the condensing reagent benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate (Py BOP) Two new cyclopeptidylpeptides, G_1 and G_2, were obtained by ring closure at 59.5% and 41.1%, respectively. The structures were confirmed by ~ 1HNMR, ~ (13) CNMR and ESI-MS. The anti-tumor activity of target compounds G_1 and G_2 was studied by MTT assay. The results showed that Galaxamide analogue G_2 with proline fragment had good cytotoxic activity, especially IC50 value of 5.85 mg / L for human breast cancer cell line MCF-7.