Lysis of Membrane Lipids Promoted by Small Organic Molecules: Reactivity Depends on Structure but not Lipophilicity

Britt, Hannah M.; Prakash, Aruna S.; Appleby, Sanna; Mosely, Jackie A.; Sanderson, John M.

doi:10.1126/sciadv.aaz8598

Lysis of Membrane Lipids Promoted by Small Organic Molecules: Reactivity Depends on Structure but not Lipophilicity

Britt, Hannah M.; Prakash, Aruna S.; Appleby, Sanna; Mosely, Jackie A.; Sanderson, John M.

Authors

Hannah M. Britt

Aruna S. Prakash

Sanna Appleby

Jackie A. Mosely

Dr John Sanderson j.m.sanderson@durham.ac.uk
Associate Professor

Abstract

Several organic molecules of low molecular weight (<150 Da) are demonstrated to have substantial membrane-lytic potential despite having a low predicted lipophilicity (logD < 1 at neutral pH). In aqueous liposome dispersions, 38 aromatic compounds were tested for their ability to either promote lipid hydrolysis or directly participate in chemical reactions with lipid molecules. Behaviors observed included acyl transfer from the lipid to form a lipidated compound, both with and without concomitant lysolipid formation; increases in the rate of lipid hydrolysis without lipidation; and no reactivity. The variation in activity, including a notably higher activity for heterocycles such as amino-substituted benzimidazoles and indazoles, demonstrates the potential to predict or “design-in” lytic activity once the rules that govern reactivity are better understood. The nature of this chemical instability has significant ramifications for the use or presence of lipids in diverse fields such as materials chemistry, food chemistry, and cell physiology.

Citation

Britt, H. M., Prakash, A. S., Appleby, S., Mosely, J. A., & Sanderson, J. M. (2020). Lysis of Membrane Lipids Promoted by Small Organic Molecules: Reactivity Depends on Structure but not Lipophilicity. Science Advances, 6(17), Article eaaz8598. https://doi.org/10.1126/sciadv.aaz8598

Journal Article Type	Article
Acceptance Date	Jan 30, 2020
Online Publication Date	Apr 22, 2020
Publication Date	Apr 22, 2020
Deposit Date	Nov 25, 2019
Publicly Available Date	May 5, 2020
Journal	Science Advances
Publisher	American Association for the Advancement of Science
Peer Reviewed	Peer Reviewed
Volume	6
Issue	17
Article Number	eaaz8598
DOI	https://doi.org/10.1126/sciadv.aaz8598

Files

Published Journal Article (274 Kb)
PDF

Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/

Copyright Statement
This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.