Click Chemistry for Drug Development and Diverse Chemical–Biology Applications

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)...

Cu-Catalyzed Click Reaction in Carbohydrate Chemistry

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.

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

Carbohydrate CuAAC click chemistry for therapy and diagnosis

Identification of diverse 1,2,3-triazole-connected benzyl glycoside-serine/threonine conjugates as potent corrosion inhibitors for mild steel in HCl

Monomeric and dimeric benzylated glycosyl benzenes were synthesized via copper-catalyzed [3 + 2] azide–alkyne cycloaddition. These compounds were then identified as protein tyrosine phosphatase (PT...

Triazole-linked Benzylated Glucosyl, Galactosyl, and Mannosyl Monomers and Dimers as Novel Sugar Scaffold-based PTP1B Inhibitors

There has been increasing interest in the development of drug candidates based on sugar templates that possess rich structural and, especially, configurational diversities We disclose herein that the epimeric identity between methyl 3,4-bis-phenylalanyl/tyrosinyl triazolyl-alpha-D-galactopyranoside and glucopyranoside may lead to their distinct inhibitory effects on specific protein tyrosine phosphatases (PTPs) Subsequently performed molecular docking study elucidated the plausible binding behaviors of the more potent galactosyl inhibitors with their primary PTP target, ie Cell Division Cycle 25B (CDC25B) phosphatase

Discovering the distinct inhibitory effects between C4-epimeric glycosyl amino acids: new insight into the development of protein tyrosine phosphatase inhibitors.

Li-Xin Gao

Papers

Triazole-linked Benzylated Glucosyl, Galactosyl, and Mannosyl Monomers and Dimers as Novel Sugar Scaffold-based PTP1B Inhibitors

Discovering the distinct inhibitory effects between C4-epimeric glycosyl amino acids: new insight into the development of protein tyrosine phosphatase inhibitors.