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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Mitochondria-penetrating peptides conjugated to desferrioxamine as chelators for mitochondrial labile iron

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Author(s):
Alta, Roxana Y. P. ; Vitorino, Hector A. ; Goswami, Dibakar ; Liria, Cleber W. ; Wisnovsky, Simon P. ; Kelley, Shana O. ; Machini, M. Teresa ; Esposito, Breno P.
Total Authors: 8
Document type: Journal article
Source: PLoS One; v. 12, n. 2 FEB 8 2017.
Web of Science Citations: 8
Abstract

Desferrioxamine (DFO) is a bacterial siderophore with a high affinity for iron, but low cell penetration. As part of our ongoing project focused on DFO-conjugates, we synthesized, purified, characterized and studied new mtDFOs (DFO conjugated to the Mitochondria Penetrating Peptides TAT(49-57), 1A, SS02 and SS20) using a succinic linker. These new conjugates retained their strong iron binding ability and antioxidant capacity. They were relatively non toxic to A2780 cells (IC50 40-100 mu M) and had good mitochondrial localization (Rr +0.45-+0.68) as observed when labeled with carboxy-tetramethylrhodamine (TAMRA) In general, mtDFO caused only modest levels of mitochondrial DNA (mtDNA) damage. DFO-SS02 retained the antioxidant ability of the parent peptide, shown by the inhibition of mitochondrial superoxide formation. None of the compounds displayed cell cycle arrest or enhanced apoptosis. Taken together, these results indicate that mtDFO could be promising compounds for amelioration of the disease symptoms of iron overload in mitochondria. (AU)

FAPESP's process: 16/03709-9 - Modulation of the levels and reactivity of physiological iron by mean of new natural or bifunctional chelators: possible applications in human health
Grantee:Breno Pannia Esposito
Support Opportunities: Regular Research Grants
FAPESP's process: 11/50318-1 - Development of compounds with pharmacological or medicinal interest and of systems for their transport, detection and recognition in biological media
Grantee:Ana Maria da Costa Ferreira
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 12/09068-4 - Microwaves, biocatalysis, divalent metal ions and nanotechnology in peptide synthesis
Grantee:Maria Teresa Machini
Support Opportunities: Regular Research Grants