The Development and Application of Clickable Lipid Analogs for Elucidating and Harnessing Lipid Functions

Best, Michael D.

doi:10.1002/9781118526996.ch4

Cited by 3 publications

(6 citation statements)

References 115 publications

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“…For this purpose, CuAAC has been proven as a helpful means for understanding and mimicking lipid functions. 494,595 The wide spectrum of applications associated with controlled functionalization of intact membrane assemblies has generated a deep interest in this field. Carbohydrate-based labeling reagents are successfully tagged with lipids via click chemistry for functionalizing the membrane surface.…”

Section: "Carbo-click" In Lipid Functionalizationmentioning

confidence: 99%

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Cu-Catalyzed Click Reaction in Carbohydrate Chemistry

et al. 2016

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Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC), popularly known as the "click reaction", serves as the most potent and highly dependable tool for facile construction of simple to complex architectures at the molecular level. Click-knitted threads of two exclusively different molecular entities have created some really interesting structures for more than 15 years with a broad spectrum of applicability, including in the fascinating fields of synthetic chemistry, medicinal science, biochemistry, pharmacology, material science, and catalysis. The unique properties of the carbohydrate moiety and the advantages of highly chemo- and regioselective click chemistry, such as mild reaction conditions, efficient performance with a wide range of solvents, and compatibility with different functionalities, together produce miraculous neoglycoconjugates and neoglycopolymers with various synthetic, biological, and pharmaceutical applications. In this review we highlight the successful advancement of Cu(I)-catalyzed click chemistry in glycoscience and its applications as well as future scope in different streams of applied sciences.

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Section: "Carbo-click" In Lipid Functionalizationmentioning

confidence: 99%

“…The importance of lipids has driven scientists toward the study of lipid functions and harnessing their valuable properties. For this purpose, CuAAC has been proven as a helpful means for understanding and mimicking lipid functions. , …”

Section: “Carbo-click” In Lipid Functionalizationmentioning

confidence: 99%

Cu-Catalyzed Click Reaction in Carbohydrate Chemistry

et al. 2016

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“…In addition, lipids are known to regulate the function of proteins that control physiological behavior of living beings through protein–membrane binding phenomena. Because of their immense biological significance, lipids and their derivatives were employed to successfully mimic membrane environments in drug delivery, gene therapy, and imaging. , In this view, as investigations aimed at understanding and mimicking lipid functions in chemical biology, modular Cu(I)-catalyzed click chemistry has been widely explored and reviewed systematically during the last 20 years. , …”

Section: Cuaac Click Chemistry Mediated Synthesis Of Diverse Glycocon...mentioning

confidence: 99%

Cu(I)-Catalyzed Click Chemistry in Glycoscience and Their Diverse Applications

et al. 2021

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Copper(I)-catalyzed 1,3-dipolar cycloaddition between organic azides and terminal alkynes, commonly known as CuAAC or click chemistry, has been identified as one of the most successful, versatile, reliable, and modular strategies for the rapid and regioselective construction of 1,4-disubstituted 1,2,3-triazoles as diversely functionalized molecules. Carbohydrates, an integral part of living cells, have several fascinating features, including their structural diversity, biocompatibility, bioavailability, hydrophilicity, and superior ADME properties with minimal toxicity, which support increased demand to explore them as versatile scaffolds for easy access to diverse glycohybrids and well-defined glycoconjugates for complete chemical, biochemical, and pharmacological investigations. This review highlights the successful development of CuAAC or click chemistry in emerging areas of glycoscience, including the synthesis of triazole appended carbohydrate-containing molecular architectures (mainly glycohybrids, glycoconjugates, glycopolymers, glycopeptides, glycoproteins, glycolipids, glycoclusters, and glycodendrimers through regioselective triazole forming modular and bio-orthogonal coupling protocols). It discusses the widespread applications of these glycoproducts as enzyme inhibitors in drug discovery and development, sensing, gelation, chelation, glycosylation, and catalysis. This review also covers the impact of click chemistry and provides future perspectives on its role in various emerging disciplines of science and technology.

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“…6–11 While initial approaches focused on the copper-catalyzed azide–alkyne cycloaddition, 12–19 this reaction suffers from some disadvantages as the required copper catalyst can promote the decomposition of lipid membranes 20 and complicate delivery in vivo. As a result, we and others have explored the application of copper-free click chemistry for lipid and membrane derivatization.…”

Section: Introductionmentioning

confidence: 99%

“…In the use of bioorthogonal derivatization for the attachment of molecules to lipids and membranes, click chemistry reactions have recently been pursued due to benefits including selectivity and fast kinetics under ambient conditions. − While initial approaches focused on the copper-catalyzed azide–alkyne cycloaddition, − this reaction suffers from some disadvantages, as the required copper catalyst can promote the decomposition of lipid membranes and complicate delivery in vivo. As a result, we and others have explored the application of copper-free click chemistry for lipid and membrane derivatization. − Examples of applications of this approach have included the attachment of thrombomodulin proteins to liposomes to enhance activity as well as the targeting of liposomes bearing trans -cyclooctene moieties to cancer cells via the pHLIP peptide for PET imaging studies …”

Section: Introductionmentioning

confidence: 99%

A Clickable and Photocleavable Lipid Analogue for Cell Membrane Delivery and Release

Alam¹,

Alves²,

Whitehead³

et al. 2015

Bioconjugate Chem.

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For drug delivery purposes, the ability to conveniently attach a targeting moiety that will deliver drugs to cells and then enable controlled release of the active molecule after localization is desirable. Towards this end, we designed and synthesized clickable and photocleavable lipid analog 1 to maximize the efficiency of bioconjugation and triggered release. This compound contains a dibenzocyclooctyne group for bioorthogonal derivatization linked via a photocleavable 2-nitrobenzyl moiety at the headgroup of a synthetic lipid backbone for targeting to cell membranes. To assess delivery and release using this system, we report fluorescence-based assays for liposomal modification and photocleavage in solution as well as through surface immobilization to demonstrate successful liposome functionalization and photoinduced release. In addition, fluorophore delivery to and release from live cells was confirmed and characterized using fluorescence microscopy and flow cytometry analysis in which 1 was delivered to cells, derivatized and photocleaved. Finally, drug delivery studies were performed using an azide-tagged analog of camptothecin, a potent anti-cancer drug that is challenging to deliver due to poor solubility. In this case, the ester attachment of the azide tag acted as a caging group for release by intracellular esterases rather than through photocleavage. This resulted in a dose-dependent response in the presence of liposomes containing delivery agent 1, confirming the ability of this compound to stimulate delivery to the cytoplasm of cells.

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The Development and Application of Clickable Lipid Analogs for Elucidating and Harnessing Lipid Functions

Cited by 3 publications

References 115 publications

Cu-Catalyzed Click Reaction in Carbohydrate Chemistry

Cu-Catalyzed Click Reaction in Carbohydrate Chemistry

Cu(I)-Catalyzed Click Chemistry in Glycoscience and Their Diverse Applications

A Clickable and Photocleavable Lipid Analogue for Cell Membrane Delivery and Release

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