Pub Date : 1900-01-01DOI: 10.1055/sos-sd-235-00184
L. J. N. Janssen, D. Blanco‐Ania
The bioorthogonal, strain-promoted azide–alkyne cycloaddition (SPAAC) and the strain-promoted alkyne–nitrone cycloaddition (SPANC) reactions have been used for conjugation with high affinity and specificity. In contrast to the cytotoxic copper-catalyzed cycloaddition, both SPAAC and SPANC are inert in biological environments. This chapter reviews the developments and applications of SPAAC and SPANC in life sciences reported since 2004, when Bertozzi et al. published the first bioorthogonal reaction.
{"title":"4.2 Applications of SPAAC and SPANC in Life Sciences","authors":"L. J. N. Janssen, D. Blanco‐Ania","doi":"10.1055/sos-sd-235-00184","DOIUrl":"https://doi.org/10.1055/sos-sd-235-00184","url":null,"abstract":"The bioorthogonal, strain-promoted azide–alkyne cycloaddition (SPAAC) and the strain-promoted alkyne–nitrone cycloaddition (SPANC) reactions have been used for conjugation with high affinity and specificity. In contrast to the cytotoxic copper-catalyzed cycloaddition, both SPAAC and SPANC are inert in biological environments. This chapter reviews the developments and applications of SPAAC and SPANC in life sciences reported since 2004, when Bertozzi et al. published the first bioorthogonal reaction.","PeriodicalId":340057,"journal":{"name":"Click Chemistry","volume":"1960 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127460410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1900-01-01DOI: 10.1055/sos-sd-235-00329
F. Friscourt
The 1,3-dipolar cycloaddition of sydnones (1,2,3-oxadiazolium-5-olates) with dipolarophiles, such as alkynes, has recently emerged as a versatile click reaction, with applications ranging from the mild and regioselective preparation of polysubstituted pyrazoles for drug discovery to the metal-free bioorthogonal ligation of biomacromolecules in living cells. This chapter reviews the importance of metal catalysis for controlling the regioselectivity of the copper-mediated reaction (CuSAC), as well as the development of fluorogenic probes, the click and release strategy, and photo-triggered ligations based on strain-promoted sydnone–alkyne cycloadditions (SPSAC).
{"title":"8 Sydnone-Based Cycloadditions in Click Chemistry","authors":"F. Friscourt","doi":"10.1055/sos-sd-235-00329","DOIUrl":"https://doi.org/10.1055/sos-sd-235-00329","url":null,"abstract":"The 1,3-dipolar cycloaddition of sydnones (1,2,3-oxadiazolium-5-olates) with dipolarophiles, such as alkynes, has recently emerged as a versatile click reaction, with applications ranging from the mild and regioselective preparation of polysubstituted pyrazoles for drug discovery to the metal-free bioorthogonal ligation of biomacromolecules in living cells. This chapter reviews the importance of metal catalysis for controlling the regioselectivity of the copper-mediated reaction (CuSAC), as well as the development of fluorogenic probes, the click and release strategy, and photo-triggered ligations based on strain-promoted sydnone–alkyne cycloadditions (SPSAC).","PeriodicalId":340057,"journal":{"name":"Click Chemistry","volume":"15 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123704165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1900-01-01DOI: 10.1055/sos-sd-235-00285
Z. Xu, K. Bratlie
Light-triggered thiol–ene polymerization is a powerful tool for synthesizing hydrogels that are aimed to be applied in situ or used as 3D scaffolds. Thiol–ene reactions are a class of click transformations that involve free-radical-mediated addition of electron-rich thiol groups to electron-poor carbon–carbon double bonds. When tuned with homopolymerization of the carbon–carbon double bonds, the resultant hydrogel properties can be finely adjusted. In this review, commonly used methods for modifying polymers with thiol groups or double bonds are discussed, and strategies to overcome flaws in thiol–ene hydrogels are provided. Emphasis is given to the application and outlook of thiol–ene cross-linked hydrogels.
{"title":"6.2 Hybridization of Thiol–Ene Chemistry Hydrogels for Biomedical Applications","authors":"Z. Xu, K. Bratlie","doi":"10.1055/sos-sd-235-00285","DOIUrl":"https://doi.org/10.1055/sos-sd-235-00285","url":null,"abstract":"Light-triggered thiol–ene polymerization is a powerful tool for synthesizing hydrogels that are aimed to be applied in situ or used as 3D scaffolds. Thiol–ene reactions are a class of click transformations that involve free-radical-mediated addition of electron-rich thiol groups to electron-poor carbon–carbon double bonds. When tuned with homopolymerization of the carbon–carbon double bonds, the resultant hydrogel properties can be finely adjusted. In this review, commonly used methods for modifying polymers with thiol groups or double bonds are discussed, and strategies to overcome flaws in thiol–ene hydrogels are provided. Emphasis is given to the application and outlook of thiol–ene cross-linked hydrogels.","PeriodicalId":340057,"journal":{"name":"Click Chemistry","volume":"189 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123750779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1900-01-01DOI: 10.1055/sos-sd-235-00062
A. La Venia, A. Kovalová, M. Vrábel
This chapter summarizes the use of the copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction in the synthesis of peptide and protein conjugates. The different reaction conditions used for construction of the conjugates and their application in various disciplines are covered. Synthetic strategies for the introduction of the click groups (azide or alkyne) into the peptide backbones are included as well.
{"title":"2.3 CuAAC in Protein Conjugation","authors":"A. La Venia, A. Kovalová, M. Vrábel","doi":"10.1055/sos-sd-235-00062","DOIUrl":"https://doi.org/10.1055/sos-sd-235-00062","url":null,"abstract":"This chapter summarizes the use of the copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction in the synthesis of peptide and protein conjugates. The different reaction conditions used for construction of the conjugates and their application in various disciplines are covered. Synthetic strategies for the introduction of the click groups (azide or alkyne) into the peptide backbones are included as well.","PeriodicalId":340057,"journal":{"name":"Click Chemistry","volume":"56 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114155479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1900-01-01DOI: 10.1055/sos-sd-235-00230
Marie-Claire Giel, C. Smedley, J. Moses
Sulfur Fluoride Exchange (SuFEx) click chemistry is a new generation technology for creating stable molecular connections with absolute reliability under metal-free conditions. SuFEx builds upon the fundamental principles of click chemistry by exploiting a unique blend of stability and latent reactivity of high oxidation state sulfur fluoride [e.g., S(VI)] functionalities to forge stable covalent linkages at connective SuFEx hubs. In this review, we focus mainly on the SuFEx hubs, sulfuryl fluoride (SO2F2), thionyl tetrafluoride (SOF4), ethenesulfonyl fluoride (ESF), 1-bromoethene-1-sulfonyl fluoride (BESF) and, 2-substituted alkyne-1-sulfonyl fluorides (SASFs). We describe each connector’s unique reactivity and their application to SuFEx click chemistry.
{"title":"5 Sulfur Fluoride Exchange (SuFEx)","authors":"Marie-Claire Giel, C. Smedley, J. Moses","doi":"10.1055/sos-sd-235-00230","DOIUrl":"https://doi.org/10.1055/sos-sd-235-00230","url":null,"abstract":"Sulfur Fluoride Exchange (SuFEx) click chemistry is a new generation technology for creating stable molecular connections with absolute reliability under metal-free conditions. SuFEx builds upon the fundamental principles of click chemistry by exploiting a unique blend of stability and latent reactivity of high oxidation state sulfur fluoride [e.g., S(VI)] functionalities to forge stable covalent linkages at connective SuFEx hubs. In this review, we focus mainly on the SuFEx hubs, sulfuryl fluoride (SO2F2), thionyl tetrafluoride (SOF4), ethenesulfonyl fluoride (ESF), 1-bromoethene-1-sulfonyl fluoride (BESF) and, 2-substituted alkyne-1-sulfonyl fluorides (SASFs). We describe each connector’s unique reactivity and their application to SuFEx click chemistry.","PeriodicalId":340057,"journal":{"name":"Click Chemistry","volume":"18 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127833635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1900-01-01DOI: 10.1055/sos-sd-235-00118
A. Paterson, T. Beke-Somfai, N. Kann
Under ruthenium catalysis, 1,5-disubstituted 1,2,3-triazoles can be accessed with high selectivity from terminal alkynes and organic azides via a ruthenium-catalyzed azide–alkyne cycloaddition (RuAAC) reaction. These conditions also allow the use of internal alkynes, providing access to 1,4,5-trisubstituted 1,2,3-triazoles. This chapter reviews the scope and limitations of the RuAAC reaction, as well as selected applications. A brief mention of azide–alkyne cycloaddition reactions catalyzed by other metals is also included.
{"title":"3 Ruthenium-Catalyzed Azide–Alkyne Cycloaddition (RuAAC)","authors":"A. Paterson, T. Beke-Somfai, N. Kann","doi":"10.1055/sos-sd-235-00118","DOIUrl":"https://doi.org/10.1055/sos-sd-235-00118","url":null,"abstract":"Under ruthenium catalysis, 1,5-disubstituted 1,2,3-triazoles can be accessed with high selectivity from terminal alkynes and organic azides via a ruthenium-catalyzed azide–alkyne cycloaddition (RuAAC) reaction. These conditions also allow the use of internal alkynes, providing access to 1,4,5-trisubstituted 1,2,3-triazoles. This chapter reviews the scope and limitations of the RuAAC reaction, as well as selected applications. A brief mention of azide–alkyne cycloaddition reactions catalyzed by other metals is also included.","PeriodicalId":340057,"journal":{"name":"Click Chemistry","volume":"58 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132123162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1900-01-01DOI: 10.1055/sos-sd-235-00082
K. Kacprzak, I. Skiera, J. Rutkowski
Proclaimed by Sharpless in 2001, the manifesto of click chemistry philosophy shifted the focus from target-oriented to drug-like-oriented synthesis, and has enormously accelerated the drug-discovery process over the last two decades. Copper(I)-catalyzed and metal-free versions of the Huisgen 1,3-dipolar cycloaddition of azides and alkynes have become the reference click chemistry synthetic tools. These processes are adaptable to various drug-design modes such as kinetic target guided synthesis (in situ click chemistry assembling; KTGS), combinatorial chemistry/high-throughput-screening approaches, or structure-based rational projecting. Moreover, the facile click chemistry derivatization of natural or synthetic products, linking molecules or improving the stability of leads by installation of 1,2,3-triazoles, is another important stream of bioactivities. This review is intended to provide a general overview of click-chemistry-powered drug design, with dozens of successful examples resulting in the discovery of nanomolar-active 1,2,3-triazoles in every stage of drug development.
{"title":"2.5 CuAAC and Metal-Free 1,3-Dipolar Huisgen Cycloadditions in Drug Discovery","authors":"K. Kacprzak, I. Skiera, J. Rutkowski","doi":"10.1055/sos-sd-235-00082","DOIUrl":"https://doi.org/10.1055/sos-sd-235-00082","url":null,"abstract":"Proclaimed by Sharpless in 2001, the manifesto of click chemistry philosophy shifted the focus from target-oriented to drug-like-oriented synthesis, and has enormously accelerated the drug-discovery process over the last two decades. Copper(I)-catalyzed and metal-free versions of the Huisgen 1,3-dipolar cycloaddition of azides and alkynes have become the reference click chemistry synthetic tools. These processes are adaptable to various drug-design modes such as kinetic target guided synthesis (in situ click chemistry assembling; KTGS), combinatorial chemistry/high-throughput-screening approaches, or structure-based rational projecting. Moreover, the facile click chemistry derivatization of natural or synthetic products, linking molecules or improving the stability of leads by installation of 1,2,3-triazoles, is another important stream of bioactivities. This review is intended to provide a general overview of click-chemistry-powered drug design, with dozens of successful examples resulting in the discovery of nanomolar-active 1,2,3-triazoles in every stage of drug development.","PeriodicalId":340057,"journal":{"name":"Click Chemistry","volume":"132 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128532462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1900-01-01DOI: 10.1055/sos-sd-235-00036
T. J. Meuleman, R. Liskamp
The tremendous recent developments in click chemistry, including the impressive developments of strain-promoted cycloaddition reagents, all started with the copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction conceived by Meldal et al. and Sharpless et al. This led to a revolution of extremely important applications in the chemical, biological, medical, and materials sciences. It is fair to state that, especially in the synthesis of multifunctional and complex small-to-large biomolecular constructs, CuAAC has been indispensable. This has been particularly evident in the area of peptides, peptidomimetics, and protein mimics. These biomolecules play key roles in the various peptide–peptide, peptide–protein, and protein–protein interactions that are involved in many diseases and disorders, and peptide-based therapeutics can be important in this context. However, it is often important to improve the bioactivity and overall stability, and modulate the spatial structure, of peptide-based therapeutics. The incorporation of the 1,4-disubstituted 1,2,3-triazole moiety as a non-native structural element using CuAAC is explored in this chapter. The resulting incorporated triazole moiety can lead to structural surrogates of the amide bond and disulfide bond. As a consequence, CuAAC can be utilized toward introducing conformational constraints and stabilizing secondary structures of α-helices, β-sheets/turns, or loop-like structures. In addition, CuAAC can be used to combine various peptide sequences with molecular scaffolds to develop protein mimics that can find applications as synthetic vaccines and antibodies.
{"title":"2.2 CuAAC in Peptidomimetics and Protein Mimics","authors":"T. J. Meuleman, R. Liskamp","doi":"10.1055/sos-sd-235-00036","DOIUrl":"https://doi.org/10.1055/sos-sd-235-00036","url":null,"abstract":"The tremendous recent developments in click chemistry, including the impressive developments of strain-promoted cycloaddition reagents, all started with the copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction conceived by Meldal et al. and Sharpless et al. This led to a revolution of extremely important applications in the chemical, biological, medical, and materials sciences. It is fair to state that, especially in the synthesis of multifunctional and complex small-to-large biomolecular constructs, CuAAC has been indispensable. This has been particularly evident in the area of peptides, peptidomimetics, and protein mimics. These biomolecules play key roles in the various peptide–peptide, peptide–protein, and protein–protein interactions that are involved in many diseases and disorders, and peptide-based therapeutics can be important in this context. However, it is often important to improve the bioactivity and overall stability, and modulate the spatial structure, of peptide-based therapeutics. The incorporation of the 1,4-disubstituted 1,2,3-triazole moiety as a non-native structural element using CuAAC is explored in this chapter. The resulting incorporated triazole moiety can lead to structural surrogates of the amide bond and disulfide bond. As a consequence, CuAAC can be utilized toward introducing conformational constraints and stabilizing secondary structures of α-helices, β-sheets/turns, or loop-like structures. In addition, CuAAC can be used to combine various peptide sequences with molecular scaffolds to develop protein mimics that can find applications as synthetic vaccines and antibodies.","PeriodicalId":340057,"journal":{"name":"Click Chemistry","volume":"42 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129703122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1900-01-01DOI: 10.1055/sos-sd-235-00143
T. Harris, I. Alabugin
This chapter discusses the creative synthetic approaches to azides and cycloalkynes, provides the rationale for controlling SPAAC reactivity through tuning cycloalkyne and azide backbone modifications, and highlights research on nitrone cycloadditions with cycloalkynes. This synthetic and knowledge toolset will help in the design of better cycloalkynes and their partners to answer challenging research questions and aid the development of new applications.
{"title":"4.1 Strain-Promoted Azide–Alkyne Cycloaddition (SPAAC): Background, Substrate Preparation, and Reactivity","authors":"T. Harris, I. Alabugin","doi":"10.1055/sos-sd-235-00143","DOIUrl":"https://doi.org/10.1055/sos-sd-235-00143","url":null,"abstract":"This chapter discusses the creative synthetic approaches to azides and cycloalkynes, provides the rationale for controlling SPAAC reactivity through tuning cycloalkyne and azide backbone modifications, and highlights research on nitrone cycloadditions with cycloalkynes. This synthetic and knowledge toolset will help in the design of better cycloalkynes and their partners to answer challenging research questions and aid the development of new applications.","PeriodicalId":340057,"journal":{"name":"Click Chemistry","volume":"28 26 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128678958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1900-01-01DOI: 10.1055/sos-sd-235-00078
A. Agrahari, A. Mishra, V. Tiwari
Copper(I)-catalyzed azide–alkyne cycloaddition reactions (CuAAC), as a versatile, reliable, and modular strategy, have been widely investigated in the area of glycoscience during the last 20 years. Herein, we presented a brief overview of CuAAC click approaches for easy access to diverse simple and complex triazole-appended carbohydrate-containing molecular architectures. Both intermolecular and intramolecular CuAAC conjugation of glycosylated azides and terminal alkynes have been widely employed for the regioselective triazole-forming reaction under standard click conditions.
{"title":"2.4 CuAAC in Carbohydrate Conjugation","authors":"A. Agrahari, A. Mishra, V. Tiwari","doi":"10.1055/sos-sd-235-00078","DOIUrl":"https://doi.org/10.1055/sos-sd-235-00078","url":null,"abstract":"Copper(I)-catalyzed azide–alkyne cycloaddition reactions (CuAAC), as a versatile, reliable, and modular strategy, have been widely investigated in the area of glycoscience during the last 20 years. Herein, we presented a brief overview of CuAAC click approaches for easy access to diverse simple and complex triazole-appended carbohydrate-containing molecular architectures. Both intermolecular and intramolecular CuAAC conjugation of glycosylated azides and terminal alkynes have been widely employed for the regioselective triazole-forming reaction under standard click conditions.","PeriodicalId":340057,"journal":{"name":"Click Chemistry","volume":"49 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131594290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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