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Identification of novel Amurin-2 variants from the skin secretion of Rana amurensis, and the design of cationicity-enhanced analogues

Author:
Zhang, Luyao, Chen, Xiaoling, Zhang, Ying, Ma, Chengbang, Xi, Xinping, Wang, Lei, Zhou, Mei, Burrows, James F., Chen, Tianbao
Source:
Biochemical and biophysical research communications 2018 v.497 pp. 943-949
ISSN:
0006-291X
Subject:
Oriental traditional medicine, Rana, antimicrobial peptides, antimicrobial properties, methicillin-resistant Staphylococcus aureus, molecular cloning, neoplasm cells, neoplasms, secretion
Abstract:
Rana amurensis is important in Chinese medicine as its skin secretions contain abundant bioactive peptides. Here, we have identified the antimicrobial peptide Amurin-2 and three highly-conserved variants, Amurin-2a, Amurin-2b and Amurin-2c through a combination of molecular cloning and MS/MS fragmentation sequencing. Synthetic replicates of these peptides demonstrate potent antimicrobial activity against S. aureus, whilst some have activity against C.albicans and even resistant bacterial MRSA. Furthermore, two Lys-analogues (K⁴-Amurin-2 and K¹¹-Amurin-2) were designed to improve the bioactive function and the antimicrobial activity of K⁴-Amurin-2 against E.coli was enhanced distinctly. In addition, the two modified peptides also showed more potent activity against S. aureus, C. albicans and MRSA strains. Meanwhile, these peptides showed inhibitory effect on the cell viability of several cancer cells. As a result, these structural and functional studies of Amurin-2 variants and analogues could provide insights for future antimicrobial peptide design.
Agid:
5915662