Discovery and analysis of a novel antimicrobial peptide B1AW from the skin secretion of Amolops wuyiensis and improving the membrane-binding affinity through the construction of the lysine-introduced analogue

Haixin Qin; Weimin Zuo; Lilin Ge; Shirley W I Siu; Lei Wang; Xiaoling Chen; Chengbang Ma; Tianbao Chen; Mei Zhou; Zhijian Cao; Hang Fai Kwok

doi:10.1016/j.csbj.2023.05.006

Discovery and analysis of a novel antimicrobial peptide B1AW from the skin secretion of Amolops wuyiensis and improving the membrane-binding affinity through the construction of the lysine-introduced analogue

Comput Struct Biotechnol J. 2023 May 6:21:2960-2972. doi: 10.1016/j.csbj.2023.05.006. eCollection 2023.

Authors

Haixin Qin^{1

2

3}, Weimin Zuo^{1

2

3}, Lilin Ge⁴, Shirley W I Siu⁵, Lei Wang⁶, Xiaoling Chen⁶, Chengbang Ma⁶, Tianbao Chen⁶, Mei Zhou⁶, Zhijian Cao⁷, Hang Fai Kwok^{1

2

3}

Affiliations

¹ Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau.
² Department of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau.
³ MoE Frontiers Science Center for Precision Oncology, University of Macau, Avenida da Universidade, Taipa, Macau.
⁴ College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
⁵ Institute of Science and Environment, University of Saint Joseph, Estrada Marginal da Ilha Verde, Macau.
⁶ School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK.
⁷ State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan 430072, China.

Abstract

In the development and study of antimicrobial peptides (AMPs), researchers have kept a watchful eye on peptides from the brevinin family because of their extensive antimicrobial activities and anticancer potency. In this study, a novel brevinin peptide was isolated from the skin secretions of the Wuyi torrent frog, Amolops wuyiensis (A. wuyiensisi), named B1AW (FLPLLAGLAANFLPQIICKIARKC). B1AW displayed anti-bacterial activity against Gram-positive bacteria Staphylococcus aureus (S. aureus), methicillin-resistant Staphylococcus aureus (MRSA), and Enterococcus faecalis (E. faecalis). B1AW-K was designed to broaden the antimicrobial spectrum of B1AW. The introduction of a lysine residue generated an AMP with enhanced broad-spectrum antibacterial activity. It also displayed the ability to inhibit the growth of human prostatic cancer PC-3, non-small lung cancer H838, and glioblastoma cancer U251MG cell lines. In molecular dynamic (MD) simulations, B1AW-K had a faster approach and adsorption to the anionic membrane than B1AW. Therefore, B1AW-K was considered a drug prototype with a dual effect, which deserves further clinical investigation and validation.

Keywords: Anticancer peptide; Antimicrobial peptide; Brevinin peptide; Molecular dynamic simulation; Peptide modification.