Design of potent, non-toxic anticancer peptides based on the structure of the antimicrobial peptide, temporin-1CEa
Design of potent, non-toxic anticancer peptides based on the structure of the antimicrobial peptide, temporin-1CEa
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DOI：
10.1007/s12272-013-0112-8
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发表时间：
2013-04
影响因子：
6.7
通讯作者：
Qing-Zhu Yang;Che Wang;L. Lang;Yang Zhou;He Wang;D. Shang
中科院分区：
文献类型：
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作者：
Qing-Zhu Yang;Che Wang;L. Lang;Yang Zhou;He Wang;D. Shang
在寻找新的抗癌药物的最新进展表明，带正电荷的抗菌肽已成为有前途的代理提供了几个优势，比传统的抗癌药物。temproin-1CEa作为一种天然存在的阳离子α-螺旋抗菌肽，已被证明具有强效的抗癌作用和中度的溶血活性。为了降低temporin-1CEa的溶血活性，提高其对多种人乳腺癌细胞的抗癌活性，本研究设计并合成了6个temporin-1CEa类似物。多肽的两亲性水平和α-螺旋结构模式得到保留，但其阳离子性和疏水性发生了变化。MTT法和溶血实验结果表明，合成的肽类化合物具有较好的抗肿瘤活性和较好的治疗指数。多肽的疏水性与其溶血活性和抗肿瘤活性呈正相关。此外，数据表明增加阳离子性同时保持天然存在的两亲性α-螺旋肽的适度疏水性的策略，以产生对肿瘤细胞具有改善的细胞毒性但对非肿瘤细胞如人红细胞具有降低的活性的类似物。这项工作突出了合理设计和合成改进的抗菌肽的潜力，这些抗菌肽具有治疗癌症的能力。
Recent advances in the search for novel anticancer agents have indicated that the positively charged antimicrobial peptides have emerged as promising agents offering several advantages over the conventional anticancer drugs. As a naturally occurring, cationic, α-helical antimicrobial peptide, temproin-1CEa has been proved to exhibit a potent anticancer effect and a moderate hemolytic activity. In order to reduce the hemolytic activity of temporin-1CEa and improve its anticancer potency towards a range of human breast cancer cells, in the present study, six analogs of temporin-1CEa were rationally designed and synthesized. The amphipathicity levels and α-helical structural patterns of peptides were reserved, while their cationic property and hydrophobicity were changed. The results of MTT and hemolysis assay indicated that the analog peptides displayed an improved anticancer activity and showed an overall optimized therapeutic index. The hydrophobicity of peptides was positively correlated with their hemolytic and antitumor activities. Moreover, the data suggest a strategy of increasing the cationicity while maintaining the moderate hydrophobicity of naturally occurring amphipathic α-helical peptides to generate analogs with improved cytotoxicity against tumor cells but decreased activity against non-neoplastic cells such as human erythrocytes. This work highlights the potential for rational design and synthesis of improved antimicrobial peptides that have the capability to be used therapeutically for treatment of cancers.