“Close-to-Release”: Spontaneous Bioorthogonal Uncaging Resulting from Ring-Closing Metathesis

Sabatino, Valerio; Rebelein, Johannes G.; Ward, Thomas R.

doi:10.1021/jacs.9b07193

Cited by 73 publications

(59 citation statements)

References 56 publications

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“…Ruthenium-, 12 − 17 palladium-, 15 − 31 gold-, 32 − 34 copper-, 35 , 36 or iron-based 37 , 38 catalysts have demonstrated their compatibility with saline aqueous solutions and their capacity to mediate chemo-specific processes in complex biological systems. The emerging field of bioorthogonal catalysis has enriched the wealth of methods available to label biomolecules, 20 , 21 release cytotoxic drugs, 14 , 17 , 24 , 26 , 38 or modulate biological functions. 15 , 16 , 23 , 31 In this context, our lab has contributed to the use of palladium (Pd) as a heterogeneous catalytic system to generate clinically approved anticancer drugs in living environs.…”

Section: Introductionmentioning

confidence: 99%

Bioorthogonal Uncaging of Cytotoxic Paclitaxel through Pd Nanosheet–Hydrogel Frameworks

et al. 2020

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The promising potential of bioorthogonal catalysis in biomedicine is inspiring incremental efforts to design strategies that regulate drug activity in living systems. To achieve this, it is not only essential to develop customized inactive prodrugs and biocompatible metal catalysts but also the right physical environment for them to interact and enable drug production under spatial and/or temporal control. Toward this goal, here, we report the first inactive precursor of the potent broad-spectrum anticancer drug paclitaxel (a.k.a. Taxol) that is stable in cell culture and labile to Pd catalysts. This new prodrug is effectively uncaged in cancer cell culture by Pd nanosheets captured within agarose and alginate hydrogels, providing a biodegradable catalytic framework to achieve controlled release of one of the most important chemotherapy drugs in medical practice. The compatibility of bioorthogonal catalysis and physical hydrogels opens up new opportunities to administer and modulate the mobility of transition metal catalysts in living environs.

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Section: Introductionmentioning

confidence: 99%

Bioorthogonal Uncaging of Cytotoxic Paclitaxel through Pd Nanosheet–Hydrogel Frameworks

et al. 2020

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“…It is also worth noting that some very interesting work in developing new bioorthogonal reactions has been reported. [147][148][149][150] Though these new reactions may not have been used in targeted drug delivery, they offer additional opportunities in this area of research. We hope that the publication of this review will provide researchers a good reference for choosing a suitable chemical linker and chemical strategies for their prodrug design, and more importantly will stimulate more research into overcoming obstacles that this field still faces in developing smart drugs for clinical applications.…”

Section: Discussionmentioning

confidence: 99%

“…In other cases, the needs for improvement may include stability and toxicity of the click partners, reaction kinetics, and side reactions with other components commonly encountered in a biological system. It is also worth noting that some very interesting work in developing new bioorthogonal reactions has been reported 147–150 . Though these new reactions may not have been used in targeted drug delivery, they offer additional opportunities in this area of research.…”

Section: Discussionmentioning

confidence: 99%

Making smart drugs smarter: The importance of linker chemistry in targeted drug delivery

Yang

Pan

Choudhury

et al. 2020

Medicinal Research Reviews

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Smart drugs, such as antibody-drug conjugates, for targeted therapy rely on the ability to deliver a warhead to the desired location and to achieve activation at the same site. Thus, designing a smart drug often requires proper linker chemistry for tethering the warhead with a vehicle in such a way that either allows the active drug to retain its potency while being tethered or ensures release and thus activation at the desired location. Recent years have seen much progress in the design of new linker activation strategies. Herein, we review the recent development of chemical strategies used to link the warhead with a delivery vehicle for preferential cleavage at the desired sites. K E Y W O R D S antibody-drug conjugates, click and release, drug delivery, linker chemistry, targeted delivery, triggered release 1 | INTRODUCTION In the world of drug discovery and development, the concept of "smart drugs" broadly refers to those that can selectively affect disease-relevant target(s). However, to a certain degree, essentially all drugs are already selective toward the desired target(s) whether they are enzyme inhibitors, receptor ligands, ion channel blockers, inhibitors of protein-protein interaction, or even genotoxins used for cancer chemotherapy, among others. They would not have made through the various milestones of drug discovery and developmental processes if they were not sufficiently selective for the intended target(s). However, once administered into the human body, the highly complex living system often leads to many unexpected off-target effects. Thus, various additional approaches have been studied and

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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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“Close-to-Release”: Spontaneous Bioorthogonal Uncaging Resulting from Ring-Closing Metathesis

Cited by 73 publications

References 56 publications

Bioorthogonal Uncaging of Cytotoxic Paclitaxel through Pd Nanosheet–Hydrogel Frameworks

Bioorthogonal Uncaging of Cytotoxic Paclitaxel through Pd Nanosheet–Hydrogel Frameworks

Making smart drugs smarter: The importance of linker chemistry in targeted drug delivery

Exploring and Adapting the Molecular Selectivity of Artificial Metalloenzymes

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