title: Identification and Characterisation of the Antimicrobial Peptide, Phylloseptin-PT, from the Skin Secretion of Phyllomedusa tarsius, and Comparison of Activity with Designed, Cationicity-Enhanced Analogues and Diastereomers.
abstract: Antimicrobial peptides belonging to the phylloseptin family are mainly found in phyllomedusine frogs. These peptides not only possess potent antimicrobial activity but exhibit low toxicity against eukaryotic cells. Therefore, they are considered as promising drug candidates for a number of diseases. In a recent study, potent antimicrobial activity was correlated with the conserved structures and cationic amphiphilic characteristics of members of this peptide family. A phylloseptin peptide precursor was discovered here in the skin secretion ofPhyllomedusa tarsiusand the mature peptide was validated by MS/MS sequencing, and was subsequently named phylloseptin-PT. The chemically-synthesized and purified phylloseptin-PT displayed activity againstStaphylococcus aureusandCandida albicans. Nevertheless, a range of cationicity-enhanced peptide analogues of phylloseptin-PT, which contained amino acid substitutions at specific sites, exhibited significant increases in antimicrobial activity compared to native phylloseptin-PT. In addition, alternative conformers which were designed and chemically-synthesized with d-lysine, showed potent antimicrobial activity and enhanced bioavailability. These data indicate that phylloseptins may represent potential candidates for next-generation antibiotics. Thus, rational design through modification of natural antimicrobial peptide templates could provide an accelerated path to overcoming obstacles en-route to their possible clinical applications.
authors.affiliation: Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK. ygao07@qub.ac.uk.
authors.forename: Yitian
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK. dwu03@qub.ac.uk.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK. x.xi@qub.ac.uk.
authors.forename: Xinping
authors.initials: X
authors.lastname: Xi
authors.affiliation: Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK. ywu16@qub.ac.uk.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK. c.ma@qub.ac.uk.
authors.forename: Chengbang
authors.initials: C
authors.lastname: Ma
authors.affiliation: Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK. m.zhou@qub.ac.uk.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK. l.wang@qub.ac.uk.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK. yangmu_831@163.com.|Liaoning Center for Certification of Drug, No.7 Chongshanxi Road, Huanggu District, Shenyang 1110036, China. yangmu_831@163.com.
authors.forename: Mu
authors.initials: M
authors.lastname: Yang
authors.affiliation: Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK. t.chen@qub.ac.uk.
authors.forename: Tianbao
authors.initials: T
authors.lastname: Chen
authors.affiliation: Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK. chris.shaw@qub.ac.uk.
authors.forename: Chris
authors.initials: C
authors.lastname: Shaw
mesh_terms: D000595:Amino Acid Sequence; D029845:Amphibian Proteins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001001:Anura; D001483:Base Sequence; D002176:Candida albicans / Q000187:drug effects; D002412:Cations; D004355:Drug Stability; D006461:Hemolysis; D006736:Horses; D008826:Microbial Sensitivity Tests; D000072756:Protein Conformation, alpha-Helical; D012867:Skin / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects; D013237:Stereoisomerism
chemical_list: D029845:Amphibian Proteins; D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; D002412:Cations
keywords: antimicrobial peptide; diastereomer; modification; phylloseptin; stability