One for the toad: Electrophysiological analysis

Skip to Navigation

Ezine

  • Published: May 15, 2019
  • Author: David Bradley
  • Channels: Chemometrics & Informatics
thumbnail image: One for the toad: Electrophysiological analysis

Molecular variegation

Photo by Marek Szczepanek from Wikimedia - https://commons.wikimedia.org/wiki/File:Bombina_variegata_(Marek_Szczepanek).jpg)

The natural products, bombinin H2 and H4, are peptides isolated from the skin of the Yellow-bellied toad, Bombina variegata, of central and southern Europe, have antimicrobial activity against Leishmania as well as bacteria. An analysis of electrophysiological data points to a possible mode of action based on pore opening, according to a study published in the journal ACS Applied Bio Materials.

The bombinins are present in the toad's skin to protect it from infection, but as with many other natural products, chemists see such physiological activity as potential for pharmaceutical development. After all, around 40 percent of all prescription drugs have an origin in natural product chemistry. Now, researchers at Tokyo University of Agriculture and Technology (TUAT) and Yokohama National University have used an analytical approach to investigate the activity of these compounds to see how the molecules disrupt lipid bilayers. The insight they provide could open up new ways to simplify the compounds for use as drugs against bacterial infection and the debilitating and potentially lethal tropical disease leishmaniasis caused by microbial trypanosomes. There are well over one million new cases of this disease each year and between 20000 and 30000 deaths.

Peptides are the bomb

Bombinin H4 is an isomer of H2, H4 having a naturally occurring D-amino acid at the end of the peptide chain, it is more potent in terms of antimicrobial activity, but exactly why was not understood until now. "D- and L-amino acids are mirror images of each other, and most amino acids in nature have the L structure," explains TUAT's Ryuji Kawano. "A few proteins are modified to have D-amino acids. The role of having D-amino acids is not fully understood in the case of [this species]."

The team carried out electrophysiological experiments with a lipid bilayer membrane to emulate a natural lipid membrane that might surround cells or a microorganism. They then analysed their data using an existing antimicrobial peptide model to see how effective these toad peptides are at disrupting the cell membrane by comparison. It turns out that the peptides punch holes in the cell membrane, which would allow the contents of a microbe to leak out and the cell die. The detailed level of activity is affected by ion permeability, the rate of pore formation, and the size of the pores formed, the team reports. It is the presence of the D-amino acid in bombinin H4 that boosts its binding affinity for the lipid membrane, and this make it more disruptive than its isomeric relative, H2.

Model insight

"These models explain well the antimicrobial activity on a molecular basis," the team writes. "Our systematic electrophysiological measurements and the signal classification analysis will contribute useful insights into the molecular mechanism of antimicrobial activities for transmembrane peptides and/or other transmembrane molecules such as synthetic channels."

Related Links

ACS Appl Bio Mater 2019, online: "Electrophysiological Analysis of Membrane Disruption by Bombinin and Its Isomer Using the Lipid Bilayer System"

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

Follow us on Twitter!

Social Links

Share This Links

Bookmark and Share

Microsites

Suppliers Selection
Societies Selection

Banner Ad

Click here to see
all job opportunities

Most Viewed

Copyright Information

Interested in separation science? Visit our sister site separationsNOW.com

Copyright © 2019 John Wiley & Sons, Inc. All Rights Reserved