Progressive design of a ranatuerin-2 peptide from Amolops wuyiensis: enhancement of bioactivity and in vivo efficacy

Aifang Yao *, Tianxing Liu, Yuhai Cai, Siqi Zhou, Xiaoling Chen, Mei Zhou, Chengbang Ma, Tianbao Chen, Chris Shaw, Lei Wang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Downloads (Pure)

Abstract

Antimicrobial peptides (AMPs) that exert multiple functions are considered promising candidates to combat the bacterial drug resistance crisis. Nowadays, targeted peptide modification has been widely recognised to improve biological activity and make up for deficiencies in clinical applications such as toxicity. In this study, a helix-loop peptide was isolated and identified from the skin secretion of the Wuyi torrent frog Amolops wuyiensis, namely, ranatuerin-2-AW (R2AW) (GFMDTAKNVAKNVAATLLDKLKCKITGGC). Target modifications were made to R2AW to study the structure–activity relationships and to optimise its bioactivities. Five analogues were progressively designed via residue substitution and truncation and the antibacterial and anticancer activities were evaluated. We found that the serine-substitution and cyclic-domain-deletion products showed similar antibacterial activity to the natural peptide R2AW, implying that the disulphide bridge and Rana box were dispensable for the antibacterial activity of ranatuerin-2 peptides. Notably, the cationicity- and hydrophobicity-enhanced variant, [Lys4,19, Leu20]R2AW(1-22)-NH2, exhibited significantly optimised antibacterial and anticancer activities. Additionally, it killed bacteria by membrane disruption at a highly efficient rate. Moreover, [Lys4,19, Leu20]R2AW(1-22)-NH2 exerted potential in vivo efficacy in a methicillin-resistant Staphylococcus aureus (MRSA)-infected waxworm model. Overall, this study demonstrated some rational design ideas for optimising the dual antibacterial and anticancer activities of ranatuerin-2 peptides and it proposes [Lys4,19, Leu20]R2AW(1-22)-NH2 as an appealing candidate for therapeutic development.
Original languageEnglish
Article number5
Number of pages22
JournalAntibiotics
Volume13
Issue number1
Early online date19 Dec 2023
DOIs
Publication statusPublished - Jan 2024

Keywords

  • antimicrobial peptides (AMPs); peptide design; multidrug-resistant bacteria; ranatuerin; drug optimisation

Fingerprint

Dive into the research topics of 'Progressive design of a ranatuerin-2 peptide from Amolops wuyiensis: enhancement of bioactivity and in vivo efficacy'. Together they form a unique fingerprint.

Cite this