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Helminth Defense Molecules as Design Templates for Membrane Active Antibiotics

Research output: Contribution to journalArticlepeer-review

K. Hammond, H. Lewis, N. Faruqui, C. Russell, B.W. Hoogenboom, M.G. Ryadnov

Original languageEnglish
Pages (from-to)1471-1479
Number of pages9
JournalACS Infectious Disease
Volume5
Issue number8
Early online date22 May 2019
DOIs
E-pub ahead of print22 May 2019
Published9 Aug 2019

Bibliographical note

Export Date: 1 July 2019

King's Authors

Abstract

A design template for membrane active antibiotics against microbial and tumor cells is described. The template is an amino acid sequence that combines the properties of helminth defense molecules, which are not cytolytic, with the properties of host-defense peptides, which disrupt microbial membranes. Like helminth defense molecules, the template folds into an amphipathic helix in both mammalian host and microbial phospholipid membranes. Unlike these molecules, the template exhibits antimicrobial and anticancer properties that are comparable to those of antimicrobial and anticancer antibiotics. The selective antibiotic activity of the template builds upon a functional synergy between three distinctive faces of the helix, which is in contrast to two faces of membrane-disrupting amphipathic structures. This synergy enables the template to adapt pore formation mechanisms according to the nature of the target membrane, inducing the lysis of microbial and tumor cells. © 2019 American Chemical Society.

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