Asayama Shoichiro, Kawamura Eri, Nagaoka Shoji, Kawakami Hiroyoshi
Department of Applied Chemistry, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji, Tokyo 192-0397, Japan.
Mol Pharm. 2006 Jul-Aug;3(4):468-70. doi: 10.1021/mp0500667.
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.
报道了一种由锰(Mn)卟啉和用于线粒体靶向的信号肽组成的新型抗氧化剂设计。所得的锰卟啉 - 寡肽共轭物表现出显著的超氧化物歧化酶(SOD)活性并能分解过氧亚硝酸盐(ONOO-)。这种新型抗氧化剂导致分离的线粒体肿胀。此外,通过使用对pH敏感的药物载体进行细胞内递送,这种新型共轭物恢复了脂多糖(LPS)刺激的巨噬细胞RAW 264.7细胞的活力。这些结果表明,经用于线粒体靶向的信号肽修饰的锰卟啉有望成为一类新型抗氧化剂。