新型露那辛衍生肽的设计、合成与抗结直肠癌活性评价  

Design,Synthesis and Evaluation of Novel Lunasin-derived Peptides for Their Anti-colorectal Cancer Activity

作　　者：陈杨强 汪小莉 CHEN Yangqiang;WANG Xiaoli(Department of Pharmacy,Anhui University of Chinese Medicine,Hefei 230012,China;Yangtze Delta Drug Advanced Research Institute,Nantong 226133,China)

机构地区：[1]安徽中医药大学药学院,安徽合肥230012 [2]长三角药物高等研究院,江苏南通226133

出　　处：《合成化学》2025年第1期48-55,共8页Chinese Journal of Synthetic Chemistry

摘　　要：基于Lunasin的截断片段E23~D43合成了6个分子(L1~L6),其中L1是对片段E23~D43进行封端修饰的母肽;根据L1,使用M27Nle突变手段合成肽L2。基于L2的α螺旋序列P21-I30和D35-D41合成了订书肽L3~L6,肽结构经MS(ESI)表征,采用CCK-8法测试目标化合物对人结直肠癌细胞株HCT-116和RKO的体外抑制活性。结果表明:与Lunasin相比,除了L5,其余化合物对HCT-116和RKO细胞的抑制效果均有提升,其中L4抑制效果最强,HCT-116 IC_(50)=5.31±0.15μM,RKO IC_(50)=4.52±0.07μM。这项研究初步证实,截断N端结构域能有效改进Lunasin的抗癌活性,尤其是对片段E23~D43的订书肽修饰,有助于提升化合物对HCT-116细胞的抑制效果。Six molecules(L1~L6)were synthesized based on the truncated Lunasin fragment E23~D43.L1 is the parent peptide with a capping modification of fragments E23~D43.L2 was synthesized with the M27Nle mutations based on L1.Stapled peptides L3 to L6 were synthesized based on theα-helical sequences P21-I30 and D35-D41 of L2.The peptide structures were characterized by MS(ESI),and the target compounds were tested for their in vitro inhibitory activity against human colorectal cancer cell lines HCT-116 and RKO using the CCK-8 assay.The results showed that,compared with Lunasin,the inhibitory activities of the other compounds,except L5,against HCT-116 and RKO cells were significantly enhanced.Among them,L4 has the strongest inhibitory effect,HCT-116 IC_(50)=5.31±0.15μM,RKO IC_(50)=4.52±0.07μM.This study preliminarily demonstrated that truncation of the N-terminal domain could enhance the anticancer activity of Lunasin,and stapled peptide modification of fragments E23~D43 helped to enhance the inhibitory effect of compounds on HCT-116 cells.

关 键 词：露那辛 结直肠癌 订书肽 抗癌肽 合成 

分 类 号：O621.3[理学—有机化学]