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• W1994379568 abstract "Limited uncoupling of oxidative phosphorylation could be beneficial for cells by preventing excessive generation of reactive oxygen species. Typical uncouplers are weak organic acids capable of permeating across membranes with a narrow gap between efficacy and toxicity. Aimed at designing a nontoxic uncoupler, the protonatable amino acid residue Glu was substituted for Val at the N-terminus of the pentadecapeptide gramicidin A (gA). The modified peptide [Glu1]gA exhibited high uncoupling activity in isolated mitochondria, in particular, abolishing membrane potential at the inner mitochondrial membrane with the same or even larger efficacy as gA. With mitochondria in cell culture, the depolarizing activity of [Glu1]gA was observed at concentrations by an order of magnitude lower than those of gA. On the contrary, [Glu1]gA was much less potent in forming proton channels in planar lipid bilayers than gA. Remarkably, at uncoupling concentrations, [Glu1]gA did not alter cell morphology and was nontoxic in MTT test, in contrast to gA showing high toxicity. The difference in the behavior of [Glu1]gA and gA in natural and artificial membranes could be ascribed to increased capability of [Glu1]gA to permeate through membranes and/or redistribute between different membranes. Based on the protective role of mild uncoupling, [Glu1]gA and some other proton-conducting gA analogues may be considered as prototypes of prospective therapeutic agents." @default.
• W1994379568 created "2016-06-24" @default.
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• W1994379568 date "2012-07-24" @default.
• W1994379568 modified "2023-09-30" @default.
• W1994379568 title "N-Terminally Glutamate-Substituted Analogue of Gramicidin A as Protonophore and Selective Mitochondrial Uncoupler" @default.
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• W1994379568 doi "https://doi.org/10.1371/journal.pone.0041919" @default.
• W1994379568 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3404012" @default.
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