Current Science

Meng Xing ¹, Xiaoxia Li , Shanshan An ¹, Chongfeng Lan ¹, Min Fu ¹, Yunfan Shi ¹, Yan Huang , Man Tang ¹, Yulin Wan ¹, Yuchuan Wang , Jingli Peng ¹, Kai Wang ¹, Zi-Wei Ye , Shaoping Weng ¹, Qiuyun Liu ¹, Jianguo He ¹, Wenliang Zhou ¹

Affiliations
1 State Key Laboratory of Biocontrol, Key Laboratory for Improved Variety Reproduction of Aquatic Economic Animals of Guangdong Province, Biomedical Center, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, CN

Abstract

The tumour specificities and potency of miniaturized cancer targeting peptides are among the major issues of current cancer research. Over 100 peptides were evaluated in this study. According to the observations, leucine could sustain the antibacterial and anticancer efficacy of (leucine/lysine)n ((L/K)n) peptides across different assay conditions, whereas (valine/lysine)n ((V/K)n) and (isoleucine/lysine)n ((I/K)n) peptides were less effective. Tumour targeting peptides, consisting of a leucine/lysine peptide and an antibody complementarity-determining region (CDR) fragment against CD47 receptor separated by a leucine₄ insulator, eradicated 100% of the lung cancer A549 cells at 100 μm concentration after 24 h of incubation. It also inhibited tumour growth in a mouse model of colon cancer cells, showing extensive apoptosis at the end of the treatment. Our data suggest that leucine insulators could be effective spacers in the design of targeted or plurispecific peptide drugs given the lack of σ –σ hyperconjugation on β -carbon and the lack of strong van der Waals interactions between the side group and the carbonyl group. Significant reduction of hemolysis by P45-3 with terminal alanine replacement on peptide P129 suggests that biosafety attribute of a peptide can be substantially improved.

Keywords

Anticancer Nanometre-Biomissiles, Antibody Complementarity-determining Region, Consensus Peptide Sequences, Leucine Insulator, Mouse Model.

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