Antitumor activity of novel chimeric peptides derived from cyclinD/CDK4 and the protein transduction domain 4
Antitumor activity of novel chimeric peptides derived from cyclinD/CDK4 and the protein transduction domain 4
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cyclinD/CDK4 和蛋白转导结构域 4 衍生的新型嵌合肽的抗肿瘤活性
DOI：
10.1007/s00726-012-1360-5
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发表时间：
2013-02-01
期刊：
影响因子：
3.5
通讯作者：
Qi, Yuanming
中科院分区：
文献类型：
--
作者：
Wang, Haili;Chen, Xi;Qi, Yuanming
cyclinD 1/CDK 4和cyclinD 3/CDK 4复合物是细胞进程的关键调节因子，因此构成了设计抗癌药物的有希望的靶点。在本研究中，从这两个复合物中选择关键肽基序。设计并合成了这些肽与蛋白转导结构域4（PTD 4）缀合的嵌合肽。PTD 4-D1、PTD 4-D3、PTD 4-K4对肿瘤细胞株具有明显的抗增殖作用。这些多肽可与cyclinD/CDK 4复合物竞争，诱导肿瘤细胞G1/S期阻滞和凋亡。在肿瘤攻击实验中，这些肽显示出有效的抗肿瘤作用，没有显著的副作用。结果表明，这些肽类化合物有望成为具有抗肿瘤活性的新型先导化合物。
CyclinD1/CDK4 and cyclinD3/CDK4 complexes are key regulators of the cell progression and therefore constitute promising targets for the design of anticancer agents. In the present study, the key peptide motifs were selected from these two complexes. Chimeric peptides with these peptides conjugated to the protein transduction domain 4 (PTD4) were designed and synthesized. The chimeric peptides, PTD4-D1, PTD4-D3, PTD4-K4 exhibited significant anti-proliferation effects on cancer cell lines. These peptides could compete with the cyclinD/CDK4 complex and induce the G1/S phase arrest and apoptosis of cancer cells. In the tumor challenge experiment, these peptides showed potent antitumor effects with no significant side effects. Our results suggested that these peptides could be served as novel leading compounds with potent antitumor activity.