Design of manganese porphyrin modified with mitochondrial signal peptide for a new antioxidant

Design of manganese porphyrin modified with mitochondrial signal peptide for a new antioxidant
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DOI:
10.1021/mp0500667
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发表时间:
2006-07-01
影响因子:
4.9
通讯作者:
Kawakami, Hiroyoshi
Kawakami, Hiroyoshi
中科院分区:
医学2区
文献类型:
--
作者:
Asayama, Shoichiro;Kawamura, Eri;Kawakami, Hiroyoshi

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报道了一种新的抗氧化剂的设计,它由锰卟啉和线粒体靶向信号肽组成。所得锰卟啉-寡肽偶联物具有显著的超氧化物歧化酶(SOD)活性和分解过氧亚硝酸根(ONOO-)。这种新的抗氧化剂引起了分离的线粒体的肿胀。此外,通过使用pH敏感的药物载体用于细胞内递送,新的缀合物恢复了脂多糖(LPS)刺激的巨噬细胞RAW 264.7细胞的活力。这些结果表明,修饰有线粒体靶向信号肽的锰卟啉有望成为一类新的抗氧化剂。
A new design of antioxidant, consisting of manganese (Mn) porphyrin and signal peptide for mitochondrial targeting, is reported. The resulting Mn-porphyrin-oligopeptide conjugate exhibited significant superoxide dismutase (SOD) activity and decomposed peroxynitrite (ONOO-). The new antioxidant caused the swelling of isolated mitochondria. By using the pH-sensitive drug carrier for intracellular delivery, furthermore, the new conjugate recovered the viability of lipopolysaccharide (LPS)-stimulated macrophage RAW 264.7 cells. These results suggest that the Mn-porphyrin modified with signal peptide for mitochondrial targeting is promising for a new class of antioxidants.