Title
Design of N-Terminal Derivatives from a Novel Dermaseptin Exhibiting Broad-Spectrum Antimicrobial Activity against Isolates from Cystic Fibrosis Patients
Author
Yuan Ying, Hui Wang, Xinping Xi, Chengbang Ma, Yue Liu, Mei Zhou, Qiang Du, James F. Burrows, Minjie Wei, Tianbao Chen, Lei Wang
Year
2019
Journal
biomolecules
Abstract
Dermaseptins are an antimicrobial peptide family widely identified from the skin secretions of phyllomeudusinae frogs. Here, we identify Dermaseptin-PC (DM-PC), from the skin secretion of Phyllomedusa coelestis, and further investigate the properties of this peptide, and a number of rationally designed truncated derivatives. The truncated 19-mer derived from the N-terminus exhibited similar antimicrobial potency when compared to the parent peptide, but the haemolytic effect of this truncated peptide was significantly decreased. Based on previous studies, the charge and hydrophobicity of truncated derivatives can affect the bioactivity of these peptides and thus we designed a 10-mer derivative with an optimised positive charge and a cyclohexylalanine (Cha) at the C-terminus for enhancing the hydrophobicity, DMPC-10A, which retained the antimicrobial activity of the parent peptide. To further investigate the influence of Cha at the C-terminus on activity, it was substituted by alanine (Ala) to generate another derivative, DMPC-10, but this was found to be much less potent. In addition, DM-PC, DMPC-19 and DMPC-10A not only rapidly killed planktonic bacteria isolated from cystic fibrosis (CF) patient, but also effectively eradicated their biofilm matrices.
Full Article
Instrument
J-815
Keywords
Circular dichroism, Secondary structure, Chemical stability, Biochemistry