Biocompatibility and therapeutic potential of glycosylated albumin artificial metalloenzymes

Eda, Shohei; Nasibullin, Igor; Vong, Kenward; Kudo, Norio; Yoshida, Minoru; Kurbangalieva, Almira; Tanaka, Katsunori

doi:10.1038/s41929-019-0317-4

Cited by 120 publications

(135 citation statements)

References 81 publications

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“…Although the development of effective intracellular catalysts based on abiotic metals remains challenging, various examples reported in the literature have tested the feasibility of this concept. [4][5][6][7][8][9][16][17][18][19][20][21][22][23][24]32 One of the most exciting opportunities of this active field of research is, however, still in its infancy: the development of devices that not only display bioorthogonal catalytic activity but are also precisely delivered to specific anatomical locations, e.g. inside tumors.…”

Section: Introductionmentioning

confidence: 99%

Cancer-derived exosomes loaded with ultrathin palladium nanosheets for targeted bioorthogonal catalysis

et al. 2019

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The transformational impact of bioorthogonal chemistries has inspired new strategies for the in vivo synthesis of bioactive agents through non-natural means. Among these, palladium (Pd) catalysts have played a prominent role in the growing subfield of bioorthogonal catalysis by producing xenobiotics and uncaging biomolecules in living systems. However, delivering catalysts selectively to specific cell types still lags behind catalyst development. Here we have developed a bio-artificial device consisting of cancer-derived exosomes loaded with Pd catalysts by a method that enables the controlled assembly of Pd nanosheets directly inside the vesicles. This hybrid system mediates Pd-triggered dealkylation reactions in vitro and inside cells and displays preferential tropism for their progenitor cells. The use of Trojan exosomes to deliver abiotic Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

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Section: Introductionmentioning

confidence: 99%

Cancer-derived exosomes loaded with ultrathin palladium nanosheets for targeted bioorthogonal catalysis

et al. 2019

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“…Using a host of different protein scaffolds (i.e. FhuA, nitrobindin, chymotrypsin streptavidin, albumin, etc), reactions have included cross metathesis, [138][139] ring-closing metathesis (RCM), 115,[139][140][141][142][143][144][145][146][147][148][149][150][151] ring-opening metathesis polymerization (ROMP), [150][151][152][153] transfer hydrogenation, [154][155][156][157][158] and alloc decaging. [159][160][161] In one study of interest, cell penetrating ArMs were devised as a method to facilitate their cellular uptake ( Figure 6A).…”

Section: New-to-nature Reactions Of Armsmentioning

confidence: 99%

Exploring and Adapting the Molecular Selectivity of Artificial Metalloenzymes

Vong

Nasibullin

Tanaka

2020

Bulletin of the Chemical Society of Japan

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In recent years, artificial metalloenzymes (ArMs) have become a major research interest in the field of biocatalysis. With the ability to facilitate new-to-nature reactions, researchers have generally prepared them either through intensive protein engineering studies or through the introduction of abiotic transition metals. The aim of this review will be to summarize the major types of ArMs that have been recently developed, as well as to highlight their general reaction scope. A point of emphasis will also be made to discuss the promising ways that the molecular selectivity of ArMs can be applied to in areas of pharmaceutical synthesis, diagnostics, and drug therapy.

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“…To address this issue, our group explored the idea of developing ArMs resistant to glutathione quenching. 90) The theory behind this approach exploited the deep hydrophobic binding pockets of albumin-based ArMs to ensure that hydrophilic metabolites (e.g., GSH) could be blocked from interacting with the embedded metal catalyst (Fig. 7).…”

Section: Arms With Abiotic Transition Metalsmentioning

confidence: 99%

“…Focusing on the anticancer agent umbelliprenin, cell-based studies successfully exhibited targeted cytotoxicity against cultures of HeLa, A549, and SW620 cells. 90) For the successful application of our GArM complexes in a therapeutic setting, our group is continuing to engage in not only improving aspects related to glycan-based targeting but also towards developing more robust and active ArMs for the selective conversion of bioactive drugs in vivo.…”

Section: Advantages Of Protein Glycosylationmentioning

confidence: 99%

Unlocking the therapeutic potential of artificial metalloenzymes

Tanaka

Vong

2020

Proceedings of the Japan Academy. Ser. B: Physical and Biologic

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In order to harness the functionality of metals, nature has evolved over billions of years to utilize metalloproteins as key components in numerous cellular processes. Despite this, transition metals such as ruthenium, palladium, iridium, and gold are largely absent from naturally occurring metalloproteins, likely due to their scarcity as precious metals. To mimic the evolutionary process of nature, the field of artificial metalloenzymes (ArMs) was born as a way to benefit from the unique chemoselectivity and orthogonality of transition metals in a biological setting. In its current state, numerous examples have successfully incorporated transition metals into a variety of protein scaffolds. Using these ArMs, many examples of new-to-nature reactions have been carried out, some of which have shown substantial biocompatibility. Given the rapid rate at which this field is growing, this review aims to highlight some important studies that have begun to take the next step within this field; namely the development of ArM-centered drug therapies or biotechnological tools.

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Biocompatibility and therapeutic potential of glycosylated albumin artificial metalloenzymes

Cited by 120 publications

References 81 publications

Cancer-derived exosomes loaded with ultrathin palladium nanosheets for targeted bioorthogonal catalysis

Cancer-derived exosomes loaded with ultrathin palladium nanosheets for targeted bioorthogonal catalysis

Exploring and Adapting the Molecular Selectivity of Artificial Metalloenzymes

Unlocking the therapeutic potential of artificial metalloenzymes

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