An Overview of Recent Advances in Biomedical Applications of Click Chemistry

Abstract

Cu(I)-catalyzed azide−alkyne cycloaddition (CuAAC) is a modular and bioorthogonal approach that is being adopted for the efficient synthesis of organic and bioorganic compounds. It leads to the selective formation of 1,4-disubstituted 1,2,3-triazole units connecting readily accessible building blocks via a stable and biocompatible linkage. The vast array of the bioconjugation applications of click chemistry has been attributed to its fast reaction kinetics, quantitative yields, minimal byproducts, and high chemospecificity and regioselectivity. These combined advantages make click reactions quite suitable for the lead identification and the development of pharmaceutical agents in the fields of medicinal chemistry and drug discovery. In this review, we have outlined the key aspects, the mechanistic details and merits and demerits of the click reaction. In addition, we have also discussed the recent pharmaceutical applications of click chemistry, ranging from the development of anticancer, antibacterial, and antiviral agents to that of biomedical imaging agents and clinical therapeutics.

Bifunctional chelators for radiorhenium: past, present and future outlook

“…201 Two excellent, up-to-date reviews by Rigolot et al and Kaur et al highlight some of the biorthogonal click chemistry methods used to target biomolecules. 203,204 The most well-known method is the copper-catalysed azide-alkyne cycloaddition (CuAAC) which forms a 1,4-disubstituted triazole, as shown in Fig. 29D.…”

Sulfoximines in Medicinal Chemistry: Emerging Trends and Opportunities from the Drug Designer’s Perspective

“…Among all the click reactions, the 1,3-dipolar cycloaddition of alkynes and azides is the most popular and has been utilized, for instance, for the development of diverse pharmaceutical and biomedical imaging agents. [58] Nevertheless, applications in the biological sciences have been somewhat limited by the requirement for copper catalysis in the click reaction [59] which thus triggered the development of a variety of alternative click reagents relying on strained triple bonds which do not require copper catalysis. However, several of these newly developed click reagents are characterized by reduced reactivity, high molecular weight and low aqueous solubility.…”

Studies of Surface Preparation for the Fluorosequencing of Peptides

“…29,30 In applications where Cu(II) may interfere with the underlying biology, the copper catalyst can be omitted by utilizing strained alkynes for surface attachment. 31 We expect this strategy to improve single-molecule fluorescence assays in which the peptide orientation and mode of coupling are important, most notably, in single-molecule protein-sequencing experiments.…”