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

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.

• 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