Characterisation of a novel peptide, Brevinin-1H, from the skin secretion of Amolops hainanensis and rational design of several analogues

As drug-resistant bacteria have become a serious health problem and have caused thousands of deaths, finding new antibiotics has become an urgent research priority. A novel antimicrobial peptide, named Brevinin-1H, was identified in the skin secretion of Amolops hainanensis through ‘shotgun’ cloning. It has broad-spectrum antimicrobial activity against tested microorganisms and has anticancer cell activity. To improve its bioactivity and decrease its cytotoxicity, two structural analogues – Brevinin-1Ha and Brevinin-1HY - were designed based on the secondary structure of the natural peptide. Brevinin-1HY, in which tyrosine substituted Pro11, had similar activity to the natural peptide against Gram-negative bacteria and cancer cells, but showed a dramatic increase in haemolytic activity and cytotoxicity at its MIC. Brevinin-1Ha, which transferred the Rana-box from the C-terminal to a central position, had significantly decreased haemolytic activity, but also in antimicrobial and anticancer activity. The present data suggests that increasing the proportion of α-helix structure in an AMP can increase its target microorganism bioactivity to some extent.