Energy migration within hexameric hemoprotein reconstituted with Zn porphyrinoid molecules

Oohora, Koji; Mashima, Tsuyoshi; Ohkubo, Kei; Fukuzumi, Shunichi; Hayashi, Takashi

doi:10.1039/c5cc02680f

Cited by 30 publications

(21 citation statements)

References 33 publications

(7 reference statements)

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“…The binding of metal complexes to proteins through supramolecular interactions or covalent modifications is of great interest in biological science . As these MTTP complexes are not water‐soluble, HSA protein encapsulation is a good strategy to dissolve them, reduce their toxicity, prolong the storage/circulation time of these drugs in blood plasma, and enhance their maximum effectiveness .…”

Section: Resultsmentioning

confidence: 99%

Metalloporphyrin Complex‐Based Nanosonosensitizers for Deep‐Tissue Tumor Theranostics by Noninvasive Sonodynamic Therapy

Chen

Cui

et al. 2018

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Metal complexes are widely used as anticancer drugs, while the severe side effects of traditional chemotherapy require new therapeutic modalities. Sonodynamic therapy (SDT) provides a significantly noninvasive ultrasound (US) treatment approach by activating sonosensitizers and initiating reactive oxygen species (ROS) to damage malignant tissues. In this work, three metal 4‐methylphenylporphyrin (TTP) complexes (MnTTP, ZnTTP, and TiOTTP) are synthesized and encapsulated with human serum albumin (HSA) to form novel nanosonosensitizers. These nanosonosensitizers generate abundant singlet oxygen (1O2) under US irradiation, and importantly show excellent US‐activatable abilities with deep‐tissue depths up to 11 cm. Compared to ZnTTP‐HSA and TiOTTP‐HSA, MnTTP‐HSA exhibits the strongest ROS‐activatable behavior due to the lowest highest occupied molecular orbital−lowest unoccupied molecular orbital gap energy by density functional theory. It is also effective for deep‐tissue photoacoustic/magnetic resonance dual‐modal imaging to trace the accumulation of nanoparticles in tumors. Moreover, MnTTP‐HSA intriguingly achieves high SDT efficiency for simultaneously suppressing the growth of bilateral tumors away from ultrasound source in mice. This work develops a deep‐tissue imaging‐guided SDT strategy through well‐defined metalloporphyrin nanocomplexes and paves a new way for highly efficient noninvasive SDT treatments of malignant tumors.

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Section: Resultsmentioning

confidence: 99%

Metalloporphyrin Complex‐Based Nanosonosensitizers for Deep‐Tissue Tumor Theranostics by Noninvasive Sonodynamic Therapy

Chen

Cui

et al. 2018

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“…Then, with the structural units, native protein oligomers and polymers may be suitable for design of metalloenzymes with multiple active sites. As exemplified recently by Hayashi and co-workers [210], the native oligomer of hexameric Tyr-coordinated heme protein (HTHP) was used as a scaffold for design of a light harvesting system. After removal of the native heme group, Zn-protoporphyrin or Zn chlorin e6 can be fully incorporated into the six heme pockets of apo-HTHP, resulting in a novel array of photosensitizers (Fig.…”

Section: In Protein Oligomers and Polymersmentioning

confidence: 99%

Rational design of metalloenzymes: From single to multiple active sites

Lin

2017

Coordination Chemistry Reviews

130

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Artificial metalloenzymes combine the advantages of both natural enzymes and chemically synthesized models, which have achieved significant progress in the last decade. This review summarizes the recent achievements in rational design of metalloenzymes from single to multiple active sites in natural or de novo protein scaffolds, with a diverse range of functionalities, even beyond those of natural metalloenzymes. These achievements include construction of mononuclear active site by metal substitution or incorporation, design of homo-or hetero-dinuclear site, introduction of Fe-sulfur or other metal clusters, reconstitution of metallo-porphyrins or other metal complexes, and design of dual or multiple active sites in single, dimeric proteins, de novo proteins, protein-protein interfaces, as well as protein oligomers and polymers. Other new trends in recent designs are also discussed. The progress not only elucidates the structural and functional relationship of natural metalloenzymes, but also provides practical clues for design of advanced artificial metalloenzymes with potential applications.

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“…The UV−vis absorption spectrum of ZnPP (6/6) HTHP V44C is similar to that of reconstituted HTHP WT with ZnPP as reported in our previous work. 50,51 As a reference sample, a protein (ZnPP (1/6) HTHP V44C ) where only one heme pocket is occupied by ZnPP was also prepared by mixing apoHTHP V44C and ZnPP (6/6) HTHP V44C with a ratio of 5:1 (Figure 9b). These obtained reconstituted proteins are described as ZnPP (n/6) HTHP V44C , where n shows the apparent number of ZnPP for HTHP having six heme pockets.…”

Section: ■ Results and Discussionmentioning

confidence: 98%

Thermoresponsive Micellar Assembly Constructed from a Hexameric Hemoprotein Modified with Poly(N-isopropylacrylamide) toward an Artificial Light-Harvesting System

et al. 2020

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Artificial protein assemblies inspired by nature have significant potential in development of emergent functional materials. In order to construct an artificial protein assembly, we employed a mutant of a thermostable hemoprotein, hexameric tyrosine-coordinated heme protein (HTHP), as a building block. The HTHP mutant which has cysteine residues introduced on the bottom surface of its columnar structure was reacted with maleimide-tethering thermoresponsive poly(N-isopropylacrylamide), PNIPAAm, to generate the protein assembly upon heating. The site-specific modification of the cysteine residues with PNIPAAm on the protein surface was confirmed by SDS-PAGE and analytical size exclusion chromatography (SEC). The PNIPAAm-modified HTHP (PNIPAAm-HTHP) is found to provide a 43 nm spherical structure at 60 °C, and the structural changes observed between the assembled and the disassembled forms were duplicated at least five times. High-speed atomic force microscopic measurements of the micellar assembly supported by cross-linkage with glutaraldehyde indicate that the protein matrices are located on the surface of the sphere and cover the inner PNIPAAm core. Furthermore, substitution of heme with a photosensitizer, Zn protoporphyrin IX (ZnPP), in the micellar assembly provides an artificial light-harvesting system. Photochemical measurements of the ZnPP-substituted micellar assembly demonstrate that energy migration among the arrayed ZnPP molecules occurs within the range of several tens of picoseconds. Our present work represents the first example of an artificial light-harvesting system based on an assembled hemoprotein oligomer structure to replicate natural light-harvesting systems.

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Energy migration within hexameric hemoprotein reconstituted with Zn porphyrinoid molecules

Cited by 30 publications

References 33 publications

Metalloporphyrin Complex‐Based Nanosonosensitizers for Deep‐Tissue Tumor Theranostics by Noninvasive Sonodynamic Therapy

Metalloporphyrin Complex‐Based Nanosonosensitizers for Deep‐Tissue Tumor Theranostics by Noninvasive Sonodynamic Therapy

Rational design of metalloenzymes: From single to multiple active sites

Thermoresponsive Micellar Assembly Constructed from a Hexameric Hemoprotein Modified with Poly(N-isopropylacrylamide) toward an Artificial Light-Harvesting System

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