| Constructing new acid-activated anticancer peptide by attaching a desirable anionic binding partner peptide | |
Zhang, Y(张云)1,2 ; Chang, Linlin1,2; Bao, Hexin1,2; Wu, Xiaoyan1,2; Liu, H(刘晖)1,2; Gou, Sanhu1,2; Zhang, Jingying1,2; Ni, JM(倪京满)1,2,3 | |
| 2022-06-01 | |
| Source Publication | JOURNAL OF DRUG TARGETING Impact Factor & Quartile |
| ISSN | 1061-186X |
| Abstract | Improving the cell selectivity of anticancer peptides (ACPs) is a major hurdle in their clinical utilisation. In this study, a new acid-activated ACP was designed by conjugating a cationic ACP LK to its anionic binding partner peptide (LEH) via a disulphide linker to trigger antitumor activity at acidic pH while masking its killing activity at normal pH. Three anionic binding peptides containing different numbers of glutamic acid (Glu) and histidine were engineered to obtain an efficient acid-activated ACP. The conjugates LK-LEH2 and LK-LEH3 exhibited 6.1- and 8.0-fold higher killing activity at pH 6.0 relative to at pH 7.4, respectively, suggesting their excellent pH-dependent antitumor activity; and their cytotoxicity was 10-fold lower than that of LK. However, LK-LEH4 had no pH-responsive killing effect. Interestingly, increasing the number of Glu from 2 to 4 increased the pH-response of the physical mixture of LK and LEH; conversely, they weakly decreased the cytotoxicity of LK, suggesting that the conjugate connection is required to achieve excellent pH dependence while maintaining minimum toxicity. LK-LEH2 and LK-LEH3 were more enzymatically stable than LK, indicating their potential for in vivo application. Our work provided a basis for designing promising ACPs with good selectivity and low toxicity. |
| Keyword | Anticancer peptide anionic binding partner acid activated low toxicity enzymatic stability |
| Publisher | TAYLOR & FRANCIS LTD |
| DOI | 10.1080/1061186X.2022.2070627 |
| Indexed By | SCIE |
| Language | 英语 |
| WOS Research Area | Pharmacology & Pharmacy |
| WOS Subject | Pharmacology & Pharmacy |
| WOS ID | WOS:000805732000001 |
| Original Document Type | Article ; Early Access |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | https://ir.lzu.edu.cn/handle/262010/480173 |
| Collection | 药学院 |
| Affiliation | 1.Lanzhou Univ, Sch Pharm, Lanzhou 730000, Peoples R China; 2.Lanzhou Univ, Sch Basic Med Sci, Key Lab Preclin Study New Drugs Gansu Prov, Lanzhou, Peoples R China; 3.Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Macau, Peoples R China |
| First Author Affilication | School of Pharmacy; School of Basic Medical Sciences |
| Recommended Citation GB/T 7714 | Zhang, Yun,Chang, Linlin,Bao, Hexin,et al. Constructing new acid-activated anticancer peptide by attaching a desirable anionic binding partner peptide[J]. JOURNAL OF DRUG TARGETING,2022. |
| APA | Zhang, Yun.,Chang, Linlin.,Bao, Hexin.,Wu, Xiaoyan.,Liu, Hui.,...&Ni, Jingman.(2022).Constructing new acid-activated anticancer peptide by attaching a desirable anionic binding partner peptide.JOURNAL OF DRUG TARGETING. |
| MLA | Zhang, Yun,et al."Constructing new acid-activated anticancer peptide by attaching a desirable anionic binding partner peptide".JOURNAL OF DRUG TARGETING (2022). |
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