| New designed pH-responsive histidine-rich peptides with antitumor activity | |
| Chang, Linlin1,2; Bao, Hexin1,2; Yao, Jia4; Liu, Hui1,2; Gou, Sanhu1,2; Zhong, Chao1,2; Zhang, Yun1,2; Ni, Jingman1,2,3 | |
| 2021-01 | |
| Online publication date | 2021-01 |
| Source Publication | JOURNAL OF DRUG TARGETING Impact Factor & Quartile |
| ISSN | 1061-186X |
| EISSN | 1029-2330 |
| Volume | 29Issue:6Pages:651-659 |
| page numbers | 9 |
| Abstract | Anticancer peptides have received widespread attention as alternative antitumor therapeutics due to their unique action mode. However, the systemic toxicity hampers their successful utilisation in tumour therapy. Here, the tumour acidic environment was used as a trigger to design a series of histidine-rich peptides by optimising the distribution of histidine and leucine based on the amphiphilic peptide LK, in hoping to achieve desirable acid-activate anticancer peptides. Among all the obtained peptides, L9H5-1 showed enhanced antitumor activity at acidic pH concomitant with low toxicity at normal pH, exhibiting excellent pH-response. At acidic pH, protonated L9H5-1 could rapidly kill tumour cells by efficient membrane disruption as evidenced by in vitro experiments, including increasing intracellular PI uptake and LDH release, dramatic membrane damage and increase of later apoptotic/necrotic cells. Moreover, no cell cycle arrest was observed after treated with L9H5-1. Interestingly, this study found that the new peptides with the same number of histidines and leucines displayed different pH-dependent antitumor activity, indicating that the position of amino acid alteration is extremely important for the design of acid-activated histidine-rich peptides. In short, our work provides a new avenue to develop new acid-activated anticancer peptides as promising antitumor drugs with high efficiency and good selectivity. |
| Keyword | Histidine-rich peptide acid-activatable antitumor high efficiency low toxicity |
| Publisher | TAYLOR & FRANCIS LTD |
| DOI | 10.1080/1061186X.2021.1873351 |
| Indexed By | SCOPUS ; SCIE |
| Language | 英语 |
| WOS Research Area | Pharmacology & Pharmacy |
| WOS Subject | Pharmacology & Pharmacy |
| WOS ID | WOS:000608890700001 |
| Original Document Type | Article |
| PMID | 33428507 |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | https://ir.lzu.edu.cn/handle/262010/449022 |
| Collection | 兰州大学 |
| Corresponding Author | Zhang, Yun; Ni, Jingman |
| Affiliation | 1.Lanzhou Univ, Sch Basic Med Sci, Key Lab Preclin Study New Drugs Gansu Prov, Lanzhou 730000, Peoples R China; 2.Lanzhou Univ, Sch Pharm, Lanzhou 730000, Peoples R China; 3.Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Macau, Peoples R China; 4.Lanzhou Univ, Hosp 1, Lanzhou, Peoples R China |
| Recommended Citation GB/T 7714 | Chang, Linlin,Bao, Hexin,Yao, Jia,et al. New designed pH-responsive histidine-rich peptides with antitumor activity[J]. JOURNAL OF DRUG TARGETING,2021,29(6):651-659. |
| APA | Chang, Linlin.,Bao, Hexin.,Yao, Jia.,Liu, Hui.,Gou, Sanhu.,...&Ni, Jingman.(2021).New designed pH-responsive histidine-rich peptides with antitumor activity.JOURNAL OF DRUG TARGETING,29(6),651-659. |
| MLA | Chang, Linlin,et al."New designed pH-responsive histidine-rich peptides with antitumor activity".JOURNAL OF DRUG TARGETING 29.6(2021):651-659. |
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