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Chemical Reviews Jun 2021Click chemistry is an immensely powerful technique for the fast and efficient covalent conjugation of molecular entities. Its broad scope has positively impacted on... (Review)
Review
Click chemistry is an immensely powerful technique for the fast and efficient covalent conjugation of molecular entities. Its broad scope has positively impacted on multiple scientific disciplines, and its implementation within the nucleic acid field has enabled researchers to generate a wide variety of tools with application in biology, biochemistry, and biotechnology. Azide-alkyne cycloadditions (AAC) are still the leading technology among click reactions due to the facile modification and incorporation of azide and alkyne groups within biological scaffolds. Application of AAC chemistry to nucleic acids allows labeling, ligation, and cyclization of oligonucleotides efficiently and cost-effectively relative to previously used chemical and enzymatic techniques. In this review, we provide a guide to inexperienced and knowledgeable researchers approaching the field of click chemistry with nucleic acids. We discuss in detail the chemistry, the available modified-nucleosides, and applications of AAC reactions in nucleic acid chemistry and provide a critical view of the advantages, limitations, and open-questions within the field.
Topics: Alkynes; Azides; Click Chemistry; Cycloaddition Reaction; Nucleic Acids; Thermodynamics
PubMed: 33443411
DOI: 10.1021/acs.chemrev.0c00928 -
Chemical Communications (Cambridge,... Apr 2022C-H Azidation is an increasingly important tool for bioconjugation, materials chemistry, and the synthesis of nitrogen-containing natural products. While several...
C-H Azidation is an increasingly important tool for bioconjugation, materials chemistry, and the synthesis of nitrogen-containing natural products. While several approaches have been developed, these often require exotic and energetic reagents, expensive photocatalysts, or both. Here we report a simple and general C-H azidation reaction using earth-abundant tetra--butylammonium decatungstate as a photocatalyst and commercial -acetamidobenzenesulfonyl azide (-ABSA) as the azide source. This system can azidate a variety of unactivated C(sp)-H bonds in moderate to good yields and excellent turnover numbers. Preliminary mechanistic experiments implicate a radical mechanism proceeding photo-hydrogen atom transfer (photo-HAT).
Topics: Azides; Catalysis; Hydrogen; Nitrogen
PubMed: 35348566
DOI: 10.1039/d2cc00425a -
Bioconjugate Chemistry Nov 2023The term "click chemistry" describes a class of organic transformations that were developed to make chemical synthesis simpler and easier, in essence allowing chemists... (Review)
Review
The term "click chemistry" describes a class of organic transformations that were developed to make chemical synthesis simpler and easier, in essence allowing chemists to combine molecular subunits as if they were puzzle pieces. Over the last 25 years, the click chemistry toolbox has swelled from the canonical copper-catalyzed azide-alkyne cycloaddition to encompass an array of ligations, including bioorthogonal variants, such as the strain-promoted azide-alkyne cycloaddition and the inverse electron-demand Diels-Alder reaction. Without question, the rise of click chemistry has impacted all areas of chemical and biological science. Yet the unique traits of radiopharmaceutical chemistry have made it particularly fertile ground for this technology. In this update, we seek to provide a comprehensive guide to recent developments at the intersection of click chemistry and radiopharmaceutical chemistry and to illuminate several exciting trends in the field, including the use of emergent click transformations in radiosynthesis, the clinical translation of novel probes synthesized using click chemistry, and the advent of click-based pretargeting.
Topics: Click Chemistry; Radiochemistry; Azides; Radiopharmaceuticals; Cycloaddition Reaction; Alkynes
PubMed: 37737084
DOI: 10.1021/acs.bioconjchem.3c00286 -
Chemical Reviews Jun 2021At its basic conceptualization, photoclick chemistry embodies a collection of click reactions that are performed via the application of light. The emergence of this... (Review)
Review
At its basic conceptualization, photoclick chemistry embodies a collection of click reactions that are performed via the application of light. The emergence of this concept has had diverse impact over a broad range of chemical and biological research due to the spatiotemporal control, high selectivity, and excellent product yields afforded by the combination of light and click chemistry. While the reactions designated as "photoclick" have many important features in common, each has its own particular combination of advantages and shortcomings. A more extensive realization of the potential of this chemistry requires a broader understanding of the physical and chemical characteristics of the specific reactions. This review discusses the features of the most frequently employed photoclick reactions reported in the literature: photomediated azide-alkyne cycloadditions, other 1,3-dipolarcycloadditions, Diels-Alder and inverse electron demand Diels-Alder additions, radical alternating addition chain transfer additions, and nucleophilic additions. Applications of these reactions in a variety of chemical syntheses, materials chemistry, and biological contexts are surveyed, with particular attention paid to the respective strengths and limitations of each reaction and how that reaction benefits from its combination with light. Finally, challenges to broader employment of these reactions are discussed, along with strategies and opportunities to mitigate such obstacles.
Topics: Alkynes; Azides; Click Chemistry; Cycloaddition Reaction; Photochemistry
PubMed: 33835796
DOI: 10.1021/acs.chemrev.0c01212 -
Molecules (Basel, Switzerland) Jun 2021Although a plethora of chemistries have been developed to selectively decorate protein molecules, novel strategies continue to be reported with the final aim of... (Review)
Review
Although a plethora of chemistries have been developed to selectively decorate protein molecules, novel strategies continue to be reported with the final aim of improving selectivity and mildness of the reaction conditions, preserve protein integrity, and fulfill all the increasing requirements of the modern applications of protein conjugates. The targeting of the protein N-terminal alpha-amine group appears a convenient solution to the issue, emerging as a useful and unique reactive site universally present in each protein molecule. Herein, we provide an updated overview of the methodologies developed until today to afford the selective modification of proteins through the targeting of the N-terminal alpha-amine. Chemical and enzymatic strategies enabling the selective labeling of the protein N-terminal alpha-amine group are described.
Topics: Amines; Azides; Binding Sites; Click Chemistry; Molecular Probe Techniques; Protein Domains; Proteins
PubMed: 34207845
DOI: 10.3390/molecules26123521 -
Molecules (Basel, Switzerland) Jun 2022In this review, we focus on some interesting and recent examples of various applications of organic azides such as their intermolecular or intramolecular, under thermal,... (Review)
Review
In this review, we focus on some interesting and recent examples of various applications of organic azides such as their intermolecular or intramolecular, under thermal, catalyzed, or noncatalyzed reaction conditions. The aforementioned reactions in the aim to prepare basic five-, six-, organometallic heterocyclic-membered systems and/or their fused analogs. This review article also provides a report on the developed methods describing the synthesis of various heterocycles from organic azides, especially those reported in recent papers (till 2020). At the outset, this review groups the synthetic methods of organic azides into different categories. Secondly, the review deals with the functionality of the azido group in chemical reactions. This is followed by a major section on the following: (1) the synthetic tools of various heterocycles from the corresponding organic azides by one-pot domino reaction; (2) the utility of the chosen catalysts in the chemoselectivity favoring C-H and C-N bonds; (3) one-pot procedures (i.e., Ugi four-component reaction); (4) nucleophilic addition, such as Aza-Michael addition; (5) cycloaddition reactions, such as [3+2] cycloaddition; (6) mixed addition/cyclization/oxygen; and (7) insertion reaction of C-H amination. The review also includes the synthetic procedures of fused heterocycles, such as quinazoline derivatives and organometal heterocycles (i.e., phosphorus-, boron- and aluminum-containing heterocycles). Due to many references that have dealt with the reactions of azides in heterocyclic synthesis (currently more than 32,000), we selected according to generality and timeliness. This is considered a recent review that focuses on selected interesting examples of various heterocycles from the mechanistic aspects of organic azides.
Topics: Amination; Azides; Catalysis; Cyclization; Cycloaddition Reaction
PubMed: 35744839
DOI: 10.3390/molecules27123716 -
ChemistryOpen Aug 2020Bioorthogonal reactions including the bioorthogonal ligations and cleavages have become an active field of research in chemical biology, and they play important roles in... (Review)
Review
Bioorthogonal reactions including the bioorthogonal ligations and cleavages have become an active field of research in chemical biology, and they play important roles in chemical modification and functional regulation of biomolecules. This review summarizes the developments and applications of the representative bioorthogonal reactions including the Staudinger reactions, the metal-mediated bioorthogonal reactions, the strain-promoted cycloadditions, the inverse electron demand Diels-Alder reactions, the light-triggered bioorthogonal reactions, and the reactions of chloroquinoxalines and -dithiophenols.
Topics: Alkynes; Azides; Catalysis; Cycloaddition Reaction; Heterocyclic Compounds, 1-Ring; Light; Metals, Heavy; Phosphines; Photolysis; Quinoxalines; Sulfhydryl Compounds
PubMed: 32817809
DOI: 10.1002/open.202000128 -
Molecules (Basel, Switzerland) Jan 2022The changes in the local and global dynamics of azide-labelled lysozyme compared with that of the wild type protein are quantitatively assessed for all alanine residues...
The changes in the local and global dynamics of azide-labelled lysozyme compared with that of the wild type protein are quantitatively assessed for all alanine residues along the polypeptide chain. Although attaching -N3 to alanine residues has been considered to be a minimally invasive change in the protein it is found that depending on the location of the alanine residue, the local and global changes in the dynamics differ. For Ala92, the change in the cross-correlated motions are minimal, whereas attaching -N3 to Ala90 leads to pronounced differences in the local and global correlations as quantified by the cross-correlation coefficients of the Cα atoms. We also demonstrate that the spectral region of the asymmetric azide stretch distinguishes between alanine attachment sites, whereas changes in the low frequency, far-infrared region are less characteristic.
Topics: Azides; Molecular Dynamics Simulation; Motion; Muramidase; Thermodynamics
PubMed: 35164105
DOI: 10.3390/molecules27030839 -
Nature Chemistry Aug 2021Chemotherapy is a powerful tool in the armoury against cancer, but it is fraught with problems due to its global systemic toxicity. Here we report the proof of concept...
Chemotherapy is a powerful tool in the armoury against cancer, but it is fraught with problems due to its global systemic toxicity. Here we report the proof of concept of a chemistry-based strategy, whereby gamma/X-ray irradiation mediates the activation of a cancer prodrug, thereby enabling simultaneous chemo-radiotherapy with radiotherapy locally activating a prodrug. In an initial demonstration, we show the activation of a fluorescent probe using this approach. Expanding on this, we show how sulfonyl azide- and phenyl azide-caged prodrugs of pazopanib and doxorubicin can be liberated using clinically relevant doses of ionizing radiation. This strategy is different to conventional chemo-radiotherapy radiation, where chemo-sensitization of the cancer takes place so that subsequent radiotherapy is more effective. This approach could enable site-directed chemotherapy, rather than systemic chemotherapy, with 'real time' drug decaging at the tumour site. As such, it opens up a new era in targeted and directed chemotherapy.
Topics: Animals; Antineoplastic Agents; Azides; Doxorubicin; Female; Fluorescent Dyes; Gamma Rays; HeLa Cells; Human Umbilical Vein Endothelial Cells; Humans; Indazoles; Mice, Inbred BALB C; Mice, Nude; Neoplasms; Oxidation-Reduction; Prodrugs; Proof of Concept Study; Pyrimidines; Sulfonamides; X-Rays; Xenograft Model Antitumor Assays; Mice
PubMed: 34112990
DOI: 10.1038/s41557-021-00711-4 -
Topics in Current Chemistry (Cham) Feb 2016In the last decade and a half, numerous bioorthogonal reactions have been developed with a goal to study biological processes in their native environment, i.e., in... (Review)
Review
In the last decade and a half, numerous bioorthogonal reactions have been developed with a goal to study biological processes in their native environment, i.e., in living cells and animals. Among them, the photo-triggered reactions offer several unique advantages including operational simplicity with the use of light rather than toxic metal catalysts and ligands, and exceptional spatiotemporal control through the application of an appropriate light source with pre-selected wavelength, light intensity and exposure time. While the photoinduced reactions have been studied extensively in materials research, e.g., on macromolecular surface, the adaptation of these reactions for chemical biology applications is still in its infancy. In this chapter, we review the recent efforts in the discovery and optimization the photo-triggered bioorthogonal reactions, with a focus on those that have shown broad utility in biological systems. We discuss in each cases the chemical and mechanistic background, the kinetics of the reactions and the biological applicability together with the limiting factors.
Topics: Alkenes; Animals; Azides; Bacterial Proteins; Click Chemistry; Cycloaddition Reaction; Light; RNA, Transfer; Tetrazoles
PubMed: 27397964
DOI: 10.1007/s41061-015-0002-2