Protonophoric and mitochondrial uncoupling activity of aryl-carbamate substituted fatty acids. Issue 1 (1st December 2022)

• Record Type: Journal Article
• Authors: MacDermott-Opeskin, Hugo; Clarke, Callum; Wu, Xin; Roseblade, Ariane; York, Edward; Pacchini, Ethan; Roy, Ritik; Cranfield, Charles; Gale, Philip A.; O'Mara, Megan L.; Murray, Michael; Rawling, Tristan
• Is Part Of: Organic & biomolecular chemistry. Volume 21:Issue 1(2022)
• Page Start: 132
• Page End: 139
• Publication Date: 2022-12-01
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/d2ob02049a
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : Aryl-carbamate substituted fatty acids are protonophores that uncouple mitochondrial oxidative phosphorylation. The proton transport cycle requires self-assembly into membrane permeable dimers. The findings demonstrate the anion transport capability of the carbamate group. 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.