Click chemistry in peptide science: a mini-review Synthesis of clickable peptides and applications
This review highlights the impact of click chemistry in peptide science. The most popular click reaction involves the reaction of an alkyne and an azide to form a rigid five membered 1, 2, 3-triazole ring under mild conditions. The triazole linkage has physico-chemical resemblance to an amide bond and is less prone to hydrolytic cleavage unlike an amide bond. Click chemistry is compatible with various protected amino acid side chains used in peptide synthesis. The simplicity, versatility and orthogonality of click reaction along with the similarity of the triazole linkage to the amide bond have been instrumental in the successful application of this reaction in peptide science. Synthesis and applications of clickable peptides are discussed in detail in this article.
Click chemistry has become a unique and efficient modern chemistry technique for chemical synthesis of complex molecules. The concept of click chemistry introduced by Professor K. B. Sharpless is similar to quickly assembling (clicking) small building blocks together to make a larger structure (1).
It was found that Huisgen Azide-Alkyne Cycloaddition reaction between an azide and an alkyne proceeds smoothly in the presence of a copper catalyst under mild conditions (Figure 1). This simple and efficient process is known as CuAAC (Copper-Catalyzed variant of Huisgen Azide-Alkyne Cycloaddition) click reaction and is the most popular and widely used click reaction. Salient features of a click reaction include stereo-specificity, simple product isolation, use of inexpensive reagents and catalysts, high efficiency, versatility and mild reaction conditions. It is also possible to carry out these reactions in polar and benign solvents such as water. The clickable functional groups are easy to incorporate into complex molecules such as peptides and are stable to oxidative conditions. Moreover these clickable groups are well tolerated under reactions involving other functional gro ...