Catalytic olefin metathesis in blood

Nasibullin, Igor; Yoshioka, Hiromasa; Mukaimine, Akari; Nakamura, Akiko; Kusakari, Yuriko; Chang, Tsung-Che; Tanaka, Katsunori

doi:10.1039/d3sc03785a

Cited by 9 publications

(6 citation statements)

References 37 publications

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“…This displays an optimization of the first coordination sphere which improved the catalyst performance in ring-closing metathesis and crossmetathesis reactions approximately by 3-fold and notably increased its stability. [54] This is an impressive result taking into account that the reaction proceeds in blood as reaction medium, conditions typically poisoning organometallic complexes.…”

Section: Case Study 1: An Arm For Olefin Metathesis With Therapeutic ...mentioning

confidence: 98%

“…The same dose of Ru-Cl@c(RGD)HSA could not stop tumor growth. [54] This publication not only highlights the significant potential of ArMs for future therapeutic application, but also displays the importance of optimizing interactions between host protein and the metal coordination sphere. In total view, it is to notice that the field of therapeutic application of ArMs is still in an early stage.…”

Section: Case Study 1: An Arm For Olefin Metathesis With Therapeutic ...mentioning

confidence: 98%

“…Tuning of this factor on the other hand can quite simply be achieved by chemically designing the first coordination sphere as also recently proven by Tanaka and coworkers. [54] Combined chemo-genetic approaches investigating cross-relationships between first coordination sphere targeted ligand design and remain rare. We believe that an increased engagement in the design of water compatible catalysts in the homogeneous catalysis community would contribute massively towards the performance of ArMs.…”

Section: Current Limitations and Possible Solutionsmentioning

confidence: 99%

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Artificial Biocatalysis: Quo Vadis?

Ingram,

Oike

2024

ChemCatChem

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Astonishing progress has been achieved in unlocking new‐to‐nature biocatalysis in the past decades. The progress in protein engineering enabled research to efficiently incorporate artificial structural elements into enzyme design. Recent trends include cofactor mimetics, artificial metalloenzymes and non‐canonical amino acids. In this perspective article, we present the state‐of‐the‐art, discuss recent examples and our view on what we call artificial biocatalysis. Although these artificial systems undoubtedly increase the scope of biocatalysis, their applicability remains challenging. Fundamental questions regarding the impact of this research field are addressed in this perspective.

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Section: Case Study 1: An Arm For Olefin Metathesis With Therapeutic ...mentioning

confidence: 98%

Section: Case Study 1: An Arm For Olefin Metathesis With Therapeutic ...mentioning

confidence: 98%

Section: Current Limitations and Possible Solutionsmentioning

confidence: 99%

See 1 more Smart Citation

Artificial Biocatalysis: Quo Vadis?

Ingram,

Oike

2024

ChemCatChem

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“…Catalysts are essential to the modern chemical industry, and novel catalysts open up avenues to new medicines 1 , materials with novel properties 2 , and more sustainable production methods 3 . To optimize reaction properties such as yield and enantiomeric excess, catalysts must be screened for compatibility and performance with each desired substrate.…”

mentioning

confidence: 99%

FACS-Sortable Triple Emulsion Picoreactors for Screening Reactions in Biphasic Environments

Thompson,

Zhang,

Yang

et al. 2024

Preprint

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Biphasic environments can enable successful chemical reactions in systems where any single solvent would be ineffective due to poor substrate solubility or poor catalyst reactivity. The broader application of biphasic reactions to screening small molecule and enzyme catalysis would be greatly enhanced by platforms for high-throughput library screening. Microfluidic droplets use pL of reagents per condition, are compatible with widely available commercial FACS machines, and are capable of processing libraries with millions of candidate catalysts. However, developing FACS-sortable droplet picoreactors compatible with biphasic screening requires optimizing solvent phases and surfactants to produce triple emulsion droplets that are < 50 microns, stable over multi-hour assays, compatible with reaction conditions, and have a shell that encapsulates the biphasic reaction core. Here, we demonstrate the generation of FACS-sortable triple emulsion picoreactors with a fluorocarbon shell and biphasic octanol-in-water core. To accomplish this, we first developed a plate reader assay and screened for surfactants that could stabilize octanol-in-water emulsions for the picoreactor core. We then demonstrated that PDMS droplet generators could produce triple emulsion droplets with the desired architecture and stability (>70% of droplets survived to 24 hours), and that proteins could be expressed via cell-free protein synthesis in the biphasic inner core. Finally, we demonstrated that these triple emulsion picoreactors can be screened, sorted, and recovered using commercial FACS sorters. These triple emulsion picoreactors have potential for screening bead-encoded catalyst libraries, including enzymes. Additionally, our droplet optimization approach is extensible to other water-immiscible organic solvents.

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“…1−4 Modification of peptides or proteins (Figure 1) has seen much study. 4c,5 Other, emerging applications include drug discovery via DNA-encoded libraries (DEL), 6,7 and in vivo metathesis in blood 8 or living cells. 9−11 Most of these applications require metathesis in water.…”

mentioning

confidence: 99%

Anionic Olefin Metathesis Catalysts Enable Modification of Unprotected Biomolecules in Water

Blanco,

Ramos Castellanos,

Fogg

2024

ACS Catal.

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Stability problems have limited the uptake of cationic olefin metathesis catalysts in chemical biology. Described herein are anionic catalysts that improve water-solubility, robustness, and compatibility with biomolecules such as DNA. A sulfonate tag is installed on the cyclic (alkyl)(amino) carbene (CAAC) ligand platform, chosen for resistance to degradation by nucleophiles, base, water, and β-elimination. Hoveyda−Grubbs catalysts bearing the sulfonated CAAC ligands deliver record productivity in metathesis of unprotected carbohydrates and nucleosides at neutral pH. Decomposed catalyst has negligible impact on metathesis selectivity, whereas N-heterocyclic carbene (NHC) catalysts degrade rapidly in water and cause extensive C=C migration.

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Catalytic olefin metathesis in blood

Abstract: A Ru-based artificial metalloenzyme (ArM) at just 1–5 mol% could catalyze olefin metathesis in blood to construct various molecular scaffolds. The cancer-targeting ArM at a low dosage could elicit tumor growth inhibition by in vivo drug synthesis.

Cited by 9 publications

References 37 publications

Artificial Biocatalysis: Quo Vadis?

Artificial Biocatalysis: Quo Vadis?

FACS-Sortable Triple Emulsion Picoreactors for Screening Reactions in Biphasic Environments

Anionic Olefin Metathesis Catalysts Enable Modification of Unprotected Biomolecules in Water

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