Site-Specific Bioconjugation and Multi-Bioorthogonal Labeling via Rapid Formation of a Boron–Nitrogen Heterocycle

Chio, Tak Ian; Gu, Han; Mukherjee, Kamalika; Tumey, L. Nathan; Bane, Susan

doi:10.1021/acs.bioconjchem.9b00246

Cited by 46 publications

(48 citation statements)

References 69 publications

(116 reference statements)

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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%

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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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Section: Discussionmentioning

confidence: 99%

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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“…Similarly, the reaction of ortho ‐acetyl phenylboronic acid ( 10 ) with carbohydrazide derivatives gives rise to a six‐membered benzodiazaborine ring (DAB, such as 13 and 14 ) . The latter shows remarkable serum stability and hydrophilicity (due to its zwitterionic nature) and for these reasons it has been mostly exploited so far for the fast assembly of highly stable bioconjugates . It is still unclear whether this functional group may also be considered as a more stable version of the traditional N ‐acylhydrazone linker, with potential applications in acid‐mediated release of potent hydrazide‐bearing anticancer drugs.…”

Section: Exploiting the Hallmarks Of Cancer: Linker Cleavage Promotedmentioning

confidence: 99%

“…dissociativeb ioorthogonal reactions), potentially releasingapayload through the so-called "click and release" mechanism. [107] The paradigm in this fieldw as introduced by Ta gworks Pharmaceuticals and it consists in the trans-cyclooctene scaffold (TCO, compound 57 in Scheme 10 A) as cleavable linker,e xploiting the fast click reactionw ith tetrazine activators (58). [108] The drug release mechanism was recently described in detail.…”

Section: Uv/vis and Nir Light-sensitive Linkersmentioning

confidence: 99%

Innovative Linker Strategies for Tumor‐Targeted Drug Conjugates

Corso

Pignataro

Belvisi

et al. 2019

Chemistry A European J

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The covalent conjugation of potent cytotoxic agents to either macromolecular carriers or small molecules represents a well‐known approach to increase the therapeutic index of these drugs, thus improving treatment efficacy and minimizing side effects. In general, cytotoxic activity is displayed only upon cleavage of a specific chemical bond (linker) that connects the drug to the carrier. The perfect balance between the linker stability and its selective cleavage represents the key for success in these therapeutic approaches and the chemical toolbox to reach this goal is continuously expanding. In this Review article, we highlight recent advances on the different modalities to promote the selective release of cytotoxic agents, either by exploiting specific hallmarks of the tumor microenvironment (e.g. pH, enzyme expression) or by the application of external triggers (e.g. light and bioorthogonal reactions).

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“…In addition to SPAAC and IEDDA, BG−BCN ( 64 in Figure 16) was shown to undergo another class of bioorthogonal cycloaddition – strain‐promoted alkyne‐nitrone cycloaddition (SPANC), [183] in the phosphorogenic activation of a nitrone‐substituted Ir(III) complex. A new class of bioorthogonal reactions that involve o ‐carbonylphenylboronic acids [184] to irreversibly afford a boronate [157c] or a diazaborine [157b,185] could work with protein/peptide tags as well. BG‐boronic acid ( 58 in Figure 16) is a successful example in utilizing SNAP‐tag to label cell surfaces via a cooperatively [186] fortified boronate [157c] …”

Section: Combining Protein/peptide Tags and Bioorthogonal Reactionsmentioning

confidence: 99%

The Collective Power of Genetically Encoded Protein/Peptide Tags and Bioorthogonal Chemistry in Biological Fluorescence Imaging

Macias-Contreras

Zhu

2020

ChemPhotoChem

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Genetically encoded protein or peptide tags and bioorthogonal chemistry are two growing classes of tools in cell biological research. A protein or peptide tag could be genetically fused to a protein of interest (POI) in the same manner as fluorescent proteins (FPs). An enzymatic ligation step would then follow to deliver a chemical entity, such as a dye or a probe with properties unattainable from FPs, to the tag, and consequently to the tethered POI. Bioorthogonal chemistry refers to a collection of (mostly) bimolecular conjugation reactions that are fine‐tuned to occur efficiently in a biological environment without the interference to or from the resident (bio)molecules or ions. These two areas of research have been developed independently and more or less concurrently. The combined use of them could expand the utilities of both tools, which is advocated in this Review. The mechanisms and utilities of protein or peptide tags and bioorthogonal chemistry are briefly reviewed separately in the first two sections, while in the third section the examples that utilize both protein or peptide tags and bioorthogonal chemistry are enumerated. Each tool and the strategy of their deployment carry their own advantages and disadvantages, and the selection of a particular tool depends on a given problem. The advances and combined use of the two topical areas are driven by the emerging challenges in illuminating the ever‐finer details of biological structures and actions.

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Site-Specific Bioconjugation and Multi-Bioorthogonal Labeling via Rapid Formation of a Boron–Nitrogen Heterocycle

Cited by 46 publications

References 69 publications

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

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

Innovative Linker Strategies for Tumor‐Targeted Drug Conjugates

The Collective Power of Genetically Encoded Protein/Peptide Tags and Bioorthogonal Chemistry in Biological Fluorescence Imaging

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