Mitochondria-penetrating peptides conjugated to desferrioxamine as chelators for mitochondrial labile iron
Mitochondria-penetrating peptides conjugated to desferrioxamine as chelators for mitochondrial labile iron
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DOI：
10.1371/journal.pone.0171729
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发表时间：
2017-02-08
期刊：
影响因子：
3.7
通讯作者：
Esposito, Breno P.
中科院分区：
文献类型：
--
作者：
Alta, Roxana Y. P.;Vitorino, Hector A.;Esposito, Breno P.
去铁胺（DFO）是一种细菌铁载体，对铁具有高亲和力，但细胞渗透性低。作为我们正在进行的专注于DFO缀合物的项目的一部分，我们使用琥珀酸接头合成、纯化、表征和研究了新的mtDFO（与线粒体穿透肽达特（49-57）、1A、SS 02和SS 20缀合的DFO）。这些新的缀合物保留了它们强的铁结合能力和抗氧化能力。它们对A2780细胞相对无毒（IC 50 40-100 μ M），并且当用羧基-四甲基罗丹明（塔姆拉）标记时观察到具有良好的线粒体定位（Rr +0.45-+0.68）。DFO-SS 02保留了亲本肽的抗氧化能力，表现为抑制线粒体超氧化物的形成。没有化合物显示细胞周期停滞或增强的凋亡。总之，这些结果表明，mtDFO可能是改善线粒体铁过载疾病症状的有前景的化合物。
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.