Screening and Structure-activity Relationship Analysis of Anti-tumor Derived Peptides Based on <i>Musca domestica</i> cecropin

doi:10.13523/j.cb.2105028

China Biotechnology

2021, Vol. 41

Issue (11): 14-22 DOI: 10.13523/j.cb.2105028

Screening and Structure-activity Relationship Analysis of Anti-tumor Derived Peptides Based on Musca domestica cecropin

DENG Rui^1,^2,³,ZENG Jia-li^1,²,LU Xue-mei^1,^2,^**(

)

1 School of Lif Science and Biopharmaceutics,Guangdong Pharmaceutical University,Guangzhou 510006,China
2 Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances,Guangzhou 510006,China
3 School of Pharmacy,Guangdong Pharmaceutical University, Guangzhou 510006,China

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Abstract

In order to find more effective, simpler, less toxic, and more stable small peptides, Musca domestica cecropin (Mdc), a housefly antimicrobial peptide cloned in our laboratory, was used to design five derived peptides and analyze the specific structure and anticancer activities of them. Based on the analysis results of Mdc, five peptides derived from the conserved sequence of Mdc were redesigned:M1-6,M1-7,M1-8,M9-21 and M27-39. Bioinformatics tools were used to predict the physical and chemical properties and secondary structure. Proliferation effects of the derived peptides on ten different cancer cell lines and the toxic effects of them on normal cells were determined by MTT assay. The safety of the five polypeptides was verified by hemolysis test and normal cytotoxicity test. Five kinds of derived peptides were designed with Mdc as template, and they all had inhibitory effects on different cancer cells. M1-7, M1-8 and M27-39 showed good activity to several kinds of cancer cells and low hemolytic activity to human erythrocytes. Interestingly, M1-7 had significant inhibitory effect on PC-12 cells, M1-8 had effective biological activity on HepG2 cells, and M27-39 had obvious inhibitory effect on HCT116 cells. The small molecular peptides with corresponding anticancer activity were successfully screened, among which M1-7, M1-8 and M27-39 have obvious specific anticancer activities and may become promising anticancer agents.

Key words： Antimicrobial peptide Musca domestica cecropin Anti-tumor activity screening Structure-activity relationship

Received: 17 May 2021 Published: 01 December 2021

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Corresponding Authors: Xue-mei LU E-mail: luxuemei@gdpu.edu.cn

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Cite this article:

DENG Rui,ZENG Jia-li,LU Xue-mei. Screening and Structure-activity Relationship Analysis of Anti-tumor Derived Peptides Based on Musca domestica cecropin. China Biotechnology, 2021, 41(11): 14-22.

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https://manu60.magtech.com.cn/biotech/10.13523/j.cb.2105028 OR https://manu60.magtech.com.cn/biotech/Y2021/V41/I11/14

Table 1 Amino acid sequence of Mdc and five derived peptides

Table 2 Results of the chemicophysical characteristics analysis of Mdc and five derived peptides

Fig.1 Sequence analysis of Mdc by ExPASY

Fig.2 Analysis of secondary structures of Mdc and five derived peptides by PyMol simulations

Fig.3 Schiffer-Edmundson wheel of Mdc and five derived peptides

Fig.4 Hydrophobicity analysis of Mdc by ExPASY

Fig.5 Effects of five derived peptides on proliferation of different cancer cells *** P<0.001, ** P<0.01, * P<0.05, as dosing groups compared with the negative control group

Fig.6 Cytotoxicity of Mdc and five derived peptides on normal cells Chang liver and NCM460

Fig.7 The effect of Mdc and five derived peptides with different concentrations on hemolysis of erythrocytes from human and mice (a) Hemolysis of erythrocytes from human (b) Hemolysis of erythrocytes from mice


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