两条肿瘤靶向抑制肽的修饰及作用靶点的初步研究

刘杰; 丁小江; 郑磊; 李前伟; 黄定德

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两条肿瘤靶向抑制肽的修饰及作用靶点的初步研究

基础医学 | 更新时间：2026-01-09

- 两条肿瘤靶向抑制肽的修饰及作用靶点的初步研究
- Modification and target study of 2 tumor targeted peptides
- 陆军军医大学学报 2016年38卷第10期页码：1096-1101
- 作者机构：
- 作者简介：
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  中图分类号： R341;R394-33;R817
- 纸质出版：2016
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刘杰,丁小江,郑磊,李前伟,黄定德.两条肿瘤靶向抑制肽的修饰及作用靶点的初步研究[J].陆军军医大学学报(原第三军医大学学报),2016,38(10):1096-1101.

　Liu Jie,Ding Xiaojiang,Zheng Lei,Li Qianwei,Huang Dingde.Modification and target study of 2 tumor targeted peptides[J].J Amry Med Univ (J Third Mil Med Univ),2016,38(10):1096-1101.
刘杰,丁小江,郑磊,李前伟,黄定德.两条肿瘤靶向抑制肽的修饰及作用靶点的初步研究[J].陆军军医大学学报(原第三军医大学学报),2016,38(10):1096-1101. DOI：

　Liu Jie,Ding Xiaojiang,Zheng Lei,Li Qianwei,Huang Dingde.Modification and target study of 2 tumor targeted peptides[J].J Amry Med Univ (J Third Mil Med Univ),2016,38(10):1096-1101. DOI：

摘要

目的探讨两条肿瘤靶向抑制肽（QKRKRKKSRKKH、RKRKRKKSRYIVLS）经化学修饰后（N端乙酰化、C端酰胺化）的稳定性，并初步探讨其作用靶点。方法

H-TdR掺入法、CCK-8法分别探讨多肽修饰前后对A549细胞增殖、活力的影响；高效液相色谱法（HPLC）测定多肽在10%血清条件下，不同时间点（12、24 h）的剩余量，评价其修饰前后在血清中的稳定性；构建GST标签的多肽（GST-多肽）融合蛋白表达载体，在大肠杆菌中诱导表达、纯化；免疫共沉淀法鉴定GST-多肽融合蛋白能否与VEGFR-1、VEGFR-2结合。结果多肽RKRKRKKSRYIVLS经化学修饰后在10%血清环境下对A549细胞增殖的抑制率由（2.63±6.19）%提高至（48.50±7.14）%（P0.01），对A549细胞活力的抑制率由（1.30±7.90）%提高至（20.80±5.90）%（P0.01），24 h后多肽在血清中的剩余量由（56.04±1.81）%提高至（64.64±0.30）%（P0.01）；多肽QKRKRKKSRKKH化学修饰前后在10%血清环境下对A549细胞增殖的抑制率分别为（28.38±5.63）%、（34.25±10.90）%（P0.05），对A549细胞活力的抑制率分别为（8.09±5.84）%、（15.07±8.09）%（P0.05），24 h后多肽在血清中的剩余量由（72.72±2.60）%提高至（77.43%±1.78）%（P0.05）；免疫共沉淀表明这两条多肽均能与VEGFR-1、VEGFR-2结合。结论 VEGFR-1、VEGFR-2为这两条肿瘤靶向抑制肽的作用靶点；多肽RKRKRK KSRYIVLS、QKRKRKKSRKKH修饰后在血清环境下稳定性明显提高，修饰后的RKRKRKKSRYIVLS对A549细胞增殖及活力的抑制能力明显增强。

Abstract

Objective To explore the stabilities of 2 tumor targeted peptides (QKRKRKKSRKKH and RKRKRKKSRYIVLS) after modification (N-terminal acetylation

C-terminal amidation) and study their targets preliminarily. Methods The effect of the peptides before and after modification on inhibiting

proliferation of A549 cells was tested by

H-TdR incorporation

and the cell vitality was explored by CCK-8 assay. The remaining peptides were tested by high-performance liquid chromatography (HPLC) in 10% serum at different time points (12 and 24 h)

and then the stability of peptides after modification could be evaluated. The expression vectors of GST-tagged peptides were constructed

and GST-peptide fused proteins were over-expressed in Escherichia coli and purified. Co-immunoprecipitation assay was used to confirm the interactions between GST-peptide fused proteins and interest receptors (VEGFR-1 and VEGFR-2). Results After modification

the inhibition ratio of RKRKRKKSRYIVLS peptide on A549 cell proliferation was increased to (48.50±7.14)% from (2.63±6.19)% (P0.01)

and the cell vitality inhibition ratio was changed to (20.80±5.90)% from (1.30±7.90)% (P0.01) in 10% serum. The remaining peptides were increased to (64.64±0.30)% from (56.04±1.81)% (P0.01) at 24 h after modification. Before and after modification

the inhibitory ratios of QKRKRKKSRKKH peptide on A549 cell proliferation were (28.38±5.63)% and (34.25±10.90)%

respectively (P0.05)

and the cell vitality inhibitory ratio were (8.09±5.84)% and (15.07±8.09)%

respectively

in 10% serum (P0.05). The remaining peptides were increased to (77.43%±1.78)% from (72.72±2.60)% (P0.05) at 24 h after modification. Co-immunoprecipitation assay confirmed that the 2 peptides could bind to VEGFR-1 and VEGFR-2. Conclusion VEGFR-1and VEGFR-2 are the targets of the 2 tumor targeted peptides. In serum

the stability of both RKRKRKKSRYIVLS peptide and QKRKRKKSRKKH peptide is enhanced significantly after modification. The inhibitory effect of RKRKRKKSRYIVLS peptide after modification on the proliferation and vitality of A549 cells is enhanced.

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