A Photoactive Carbon-Monoxide-Releasing Protein Cage for Dose-Regulated Delivery in Living Cells

被引:70
作者
Fujita, Kenta [1 ]
Tanaka, Yuya [2 ]
Abe, Satoshi [1 ]
Ueno, Takafumi [1 ]
机构
[1] Tokyo Inst Technol, Grad Sch Biosci & Biotechnol, Dept Biomol Engn, Midori Ku, Yokohama, Kanagawa 2268501, Japan
[2] Tokyo Inst Technol, Chem Resources Lab, Midori Ku, Yokohama, Kanagawa 226850, Japan
关键词
bioinorganic chemistry; carbon monoxide; metalloproteins; photoactivation; protein engineering; APO-FERRITIN; CO RELEASE; PHOTODYNAMIC THERAPY; DESIGN STRATEGIES; COMPLEXES; MOLECULES; NANOPARTICLES; MANGANESE; LIGHT; COORDINATION;
D O I
10.1002/anie.201506738
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Protein cages can serve as bioinorganic molecular templates for functionalizing metal compounds to regulate cellular signaling. We succeeded in developing a photoactive CO-releasing system by constructing a composite of ferritin (Fr) containing manganese-carbonyl complexes. When Arg52 adjacent to Cys48 of Fr is replaced with Cys, the Fr mutant stabilizes the retention of 48Mn-carbonyl moieties, which can release the CO ligands under light irradiation, although wild-type Fr retains very few Mn moieties. The amount of released CO is regulated by the extent of irradiation. This could reveal an optimized dose for cooperatively activating the nuclear factor B (NF-B) in mammalian cells and the tumor necrosis factor (TNF-). These results suggest that construction of a CO-releasing protein cage will advance of research in CO biology.
引用
收藏
页码:1056 / 1060
页数:5
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