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

• Published in: Angewandte Chemie International Edition Vol. 55; no. 3; pp. 1056 - 1060
• Main Authors: Fujita, Kenta, Tanaka, Yuya, Abe, Satoshi, Ueno, Takafumi
• Format: Journal Article
• Language: English
• Published: Germany Blackwell Publishing Ltd 18-01-2016; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: bioinorganic chemistry; Biology; Cages; Carbon; Carbon monoxide; Carbon Monoxide - chemistry; Carbonyls; Cells (biology); Composite materials; Construction; Drug Carriers; Ferritin; Irradiation; Ligands; Light effects; Light irradiation; Lymphocytes B; Mammalian cells; Mammals; Manganese; Metal compounds; metalloproteins; Metals; NF-κB protein; NFKB1 protein; photoactivation; protein engineering; Proteins; Proteins - chemistry; Releasing; Retention; Rodents; Tumor necrosis factor; Tumor necrosis factor-TNF; carbon monoxide; protein engineering; photoactivation; metalloproteins; bioinorganic chemistry
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201506738

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 48 Mn–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 κB (NF‐κB) in mammalian cells and the tumor necrosis factor α (TNF‐α). These results suggest that construction of a CO‐releasing protein cage will advance of research in CO biology.
Photoactivable protein cage: A ferritin protein cage retaining manganese–carbonyl complexes released carbon monoxide (CO; see picture) under visible‐light irradiation. The amount of released CO is modulated by the irradiation period. The system showed an optimized CO dose for activating a cellular transcriptional factor.