Click chemistry

The amine- and thiol-reactive labeling chemistries described in in situ labeling of total cellular thiol or amine content. In situ labeling of specific molecular populations—such as proteins and nucleic acids that have been newly synthesized in some experimental time window of interest—is not feasible due to the ubiquitous distribution of amines and thiols in cells, as well as in the media in which they are maintained. Invitrogen™ Click-iT™ labeling technology overcomes this obstacle by employing bioorthogonal reactive chemistry, in which the reaction partners have no endogenous representation in biological molecules, cells, tissues or model organisms. In addition to reaction selectivity, in situ labeling methods should allow reactivity under mild conditions and in predominantly aqueous solvent conditions. Although several known chemistries fulfill the requirements described above, Click-iT labeling technology is founded upon one of the most successful and versatile bioorthogonal labeling reactions currently available—the copper-catalyzed azide–alkyne ( Figure 3.1.1). Application of this reaction to in situ labeling of cells is a two-step process. First, one reaction partner—either an azide or alkyne linked to a "building block" such as a nucleotide, nucleoside, amino acid, monosaccharide or fatty acid—is biosynthetically incorporated. Subsequently, the other reaction partner—the complementary alkyne or azide linked to a fluorescent dye, biotin or other d...

Further Information Related Reactions Click Chemistry Azide-Alkyne Cycloaddition "Click Chemistry" is a term that was introduced by K. B. Sharpless in 2001 to describe reactions that are high yielding, wide in scope, create only byproducts that can be removed without chromatography, are stereospecific, simple to perform, and can be conducted in easily removable or benign solvents. This concept was developed in parallel with the interest within the pharmaceutical, materials, and other industries in capabilities for generating large libraries of compounds for screening in discovery research. Several types of reaction have been identified that fulfill these criteria, thermodynamically-favored reactions that lead specifically to one product, such as nucleophilic ring opening reactions of epoxides and aziridines, non-aldol type carbonyl reactions, such as formation of hydrazones and heterocycles, additions to carbon-carbon multiple bonds, such as oxidative formation of epoxides and For example, an examination of the azide-alkyne cycloaddition shows that it fulfills many of the prerequisites. Many of the starting monosubstituted alkynes and organic azides are available commercially, many others can easily be synthesized with a wide range of functional groups, and their cycloaddition reaction selectively gives 1,2,3-triazoles. Unfortunately, the thermal Mechanism of the Huisgen Azide-Alkyne 1,3-Dipolar Cycloaddition For the mechanism, please refer to the text on V. V. Rostovtsev,...

Small molecule reactions allowing the joining of substrates of choice with specific biomolecules In click chemistry is a class of simple, atom-economy reactions commonly used for joining two molecular entities of choice. Click chemistry is not a single specific reaction, but describes a way of generating products that follow examples in Click reactions occur in By developing specific and controllable The term "click chemistry" was coined by Background [ ] Click chemistry is a method for attaching a One of the earliest and most important methods in bioconjugation was to express a reporter on the same To overcome these challenges, chemists have opted to proceed by identifying pairs of Now limitations emerge from the chemistry of the probe to its target. In order for this technique to be useful in biological systems, click chemistry must run at or near biological conditions, produce little and (ideally) non-toxic byproducts, have (preferably) single and stable products at the same conditions, and proceed quickly to high yield in Biotech company Reactions [ ] For a reaction to be considered a click reaction, it must satisfy certain characteristics: • modularity • insensitivity to solvent parameters • high • insensitivity towards oxygen and water • regiospecificity and • a large thermodynamic driving force (>20 The process would preferably: • have simple reaction conditions • use readily available starting materials and reagents • use no solvent or use a solvent that is benign ...

But how exactly does it work? Imagine two people walking through a mostly empty room towards each other then shaking hands. "That's how a classical chemical reaction is done," said Benjamin Schumann, a chemist at Imperial College London. But what if there was lots of furniture and other people clogging up the room? "They might not meet each other," Schumann said. Now imagine those people were molecules, tiny groups of atoms that form the basis of chemistry. "Click chemistry makes it possible for two molecules that are in an environment where you have lots of other things around" to meet and join with each other, he told AFP. The way But Carolyn Bertozzi, who shared this year's chemistry Nobel with Barry Sharpless and Morten Meldal, said it would take a very special kind of Lego. Even if two Legos were "surrounded by millions of other very similar plastic toys" they would only click in to each other, she told AFP. Nobel Prize in Chemistry 2022. 'Changed the playing field' Around the year 2000, Sharpless and Meldal separately discovered a specific chemical reaction using copper ions as a catalyst which "changed the playing field" and became "the cream of the crop", said Silvia Diez-Gonzalez, a chemist at Imperial College London. Copper has many advantages, including that reactions could involve water and be done at This particular way of connecting molecules was far more flexible, efficient and targeted than had ever been possible before. Since its discovery, chemists have b...

Nucleic acids play crucial roles in transferring cellular information and gene regulations. DNA and RNA molecules have been associated with multiple human diseases and thus offer opportunities for exploring small molecule-based therapeutics. However, developing target-selective molecules possessing well-defined biological activity, has always been challenging. In the current scenario, where the world is continuously experiencing outbreaks of new infectious diseases, it is always important to expand the scope of chemical toolsets to override conventional drug discovery strategies for developing therapeutically relevant drug candidates. The template-directed synthetic approach has emerged as a promising tool for rapid drug discovery. It allows a biological target to template the selection or synthesis of its ligands from a pool of reactive fragments. There are two main template-directed synthetic strategies: thermodynamically controlled dynamic combinatorial chemistry (DCC) and kinetically controlled target-guided in situ click chemistry. Though discovered only two decades ago, these techniques have proven their usefulness for nucleic acid targets, as exemplified by the increasing number of applications with therapeutically important DNA and RNA targets. However, nucleic acid templated synthetic techniques are relatively unexplored in drug discovery compared to protein targets. In this review article, we have presented a detailed discussion of all the reported nucleic acid t...