Protonophoric and mitochondrial uncoupling activity of aryl-carbamate substituted fatty acids.

MacDermott-Opeskin, H; Clarke, C; Wu, X; Roseblade, A; York, E; Pacchini, E; Roy, R; Cranfield, C; Gale, PA; O'Mara, ML; Murray, M; Rawling, T

Protonophoric and mitochondrial uncoupling activity of aryl-carbamate substituted fatty acids.

MacDermott-Opeskin, H Clarke, C Wu, X Roseblade, A York, E Pacchini, E Roy, R Cranfield, C

Gale, PA O'Mara, ML Murray, M Rawling, T

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Publisher:: Royal Society of Chemistry
Publication Type:: Journal Article
Citation:: Organic and Biomolecular Chemistry, 2023, 21, (1), pp. 132-139
Issue Date:: 2023-12-21

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Field	Value	Language
dc.contributor.author	MacDermott-Opeskin, H
dc.contributor.author	Clarke, C
dc.contributor.author	Wu, X
dc.contributor.author	Roseblade, A
dc.contributor.author	York, E
dc.contributor.author	Pacchini, E
dc.contributor.author	Roy, R
dc.contributor.author	Cranfield, C https://orcid.org/0000-0003-3608-5440
dc.contributor.author	Gale, PA
dc.contributor.author	O'Mara, ML
dc.contributor.author	Murray, M
dc.contributor.author	Rawling, T https://orcid.org/0000-0002-6624-6586
dc.date.accessioned	2023-09-27T04:52:10Z
dc.date.available	2023-09-27T04:52:10Z
dc.date.issued	2023-12-21
dc.identifier.citation	Organic and Biomolecular Chemistry, 2023, 21, (1), pp. 132-139
dc.identifier.issn	1477-0520
dc.identifier.issn	1477-0539
dc.identifier.uri	http://hdl.handle.net/10453/172329
dc.description.abstract	Aryl-urea substituted fatty acids are protonophores and mitochondrial uncouplers that utilise a urea-based synthetic anion transport moiety to carry out the protonophoric cycle. Herein we show that replacement of the urea group with carbamate, a functional group not previously reported to possess anion transport activity, produces analogues that retain the activity of their urea counterparts. Thus, the aryl-carbamate substituted fatty acids uncouple oxidative phosphorylation and inhibit ATP production by collapsing the mitochondrial proton gradient. Proton transport proceeds via self-assembly of the deprotonated aryl-carbamates into membrane permeable dimeric species, formed by intermolecular binding of the carboxylate group to the carbamate moiety. These results highlight the anion transport capacity of the carbamate functional group.
dc.format	Electronic
dc.language	eng
dc.publisher	Royal Society of Chemistry
dc.relation	http://purl.org/au-research/grants/arc/DP200100453
dc.relation.ispartof	Organic and Biomolecular Chemistry
dc.relation.isbasedon	10.1039/d2ob02049a
dc.rights	info:eu-repo/semantics/embargoedAccess
dc.subject	0304 Medicinal and Biomolecular Chemistry, 0305 Organic Chemistry
dc.subject.classification	Organic Chemistry
dc.subject.classification	3404 Medicinal and biomolecular chemistry
dc.subject.classification	3405 Organic chemistry
dc.subject.mesh	Carbamates
dc.subject.mesh	Fatty Acids
dc.subject.mesh	Mitochondria
dc.subject.mesh	Oxidative Phosphorylation
dc.subject.mesh	Protons
dc.subject.mesh	Fatty Acids
dc.subject.mesh	Protons
dc.subject.mesh	Carbamates
dc.subject.mesh	Mitochondria
dc.subject.mesh	Oxidative Phosphorylation
dc.subject.mesh	Mitochondria
dc.subject.mesh	Protons
dc.subject.mesh	Carbamates
dc.subject.mesh	Fatty Acids
dc.subject.mesh	Oxidative Phosphorylation
dc.subject.mesh	Fatty Acids
dc.subject.mesh	Protons
dc.subject.mesh	Carbamates
dc.subject.mesh	Mitochondria
dc.subject.mesh	Oxidative Phosphorylation
dc.title	Protonophoric and mitochondrial uncoupling activity of aryl-carbamate substituted fatty acids.
dc.type	Journal Article
utslib.citation.volume	21
utslib.location.activity	England
utslib.for	0304 Medicinal and Biomolecular Chemistry
utslib.for	0305 Organic Chemistry
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
pubs.organisational-group	/University of Technology Sydney/Centre for Health Technologies (CHT)
pubs.organisational-group	/University of Technology Sydney/Strength - TKC - The Kidman Centre
utslib.copyright.status	open_access	*
pubs.consider-herdc	false
utslib.copyright.embargo	2024-01-01T00:00:00+1000Z
dc.date.updated	2023-09-27T04:52:09Z
pubs.issue	1
pubs.publication-status	Published online
pubs.volume	21
utslib.citation.issue	1

Abstract:

Aryl-urea substituted fatty acids are protonophores and mitochondrial uncouplers that utilise a urea-based synthetic anion transport moiety to carry out the protonophoric cycle. Herein we show that replacement of the urea group with carbamate, a functional group not previously reported to possess anion transport activity, produces analogues that retain the activity of their urea counterparts. Thus, the aryl-carbamate substituted fatty acids uncouple oxidative phosphorylation and inhibit ATP production by collapsing the mitochondrial proton gradient. Proton transport proceeds via self-assembly of the deprotonated aryl-carbamates into membrane permeable dimeric species, formed by intermolecular binding of the carboxylate group to the carbamate moiety. These results highlight the anion transport capacity of the carbamate functional group.

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http://hdl.handle.net/10453/172329