Design of manganese porphyrin modified with mitochondrial signal peptide for a new antioxidant.
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.
Asayama
Shoichiro
S
Department of Applied Chemistry, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji, Tokyo 192-0397, Japan. asayama-shoichiro@c.metro-u.ac.jp
Kawamura
Eri
E
Nagaoka
Shoji
S
Kawakami
Hiroyoshi
H
D000595:Amino Acid Sequence; D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D015195:Drug Design; D066298:In Vitro Techniques; D007700:Kinetics; D008345:Manganese / Q000737:chemistry; D008665:Metalloporphyrins / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects; D008933:Mitochondrial Swelling / Q000187:drug effects; D008969:Molecular Sequence Data; D015394:Molecular Structure; D030421:Peroxynitrous Acid / Q000378:metabolism; D021382:Protein Sorting Signals / Q000235:genetics; D011524:Protoporphyrins; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D008665:Metalloporphyrins; D021382:Protein Sorting Signals; D011524:Protoporphyrins; D030421:Peroxynitrous Acid; C038654:manganese protoporphyrin; D008345:Manganese; D013482:Superoxide Dismutase