Amide bonds are the most prevalent structures found in organic molecules and various biomolecules such as peptides, proteins, DNA, and RNA. The unique feature of amide bonds is their ability to form resonating structures, thus, they are highly stable and adopt particular three-dimensional structures, which, in turn, are responsible for their functions. The main focus of this review article is to report the methodologies for the activation of the unactivated amide bonds present in biomolecules, which includes the enzymatic approach, metal complexes, and non-metal based methods. This article also discusses some of the applications of amide bond activation approaches in the sequencing of proteins and the synthesis of peptide acids, esters, amides, and thioesters.

Proteome profiling by activated esters identified > 9000 ligandable lysines but they are limited as covalent inhibitors due to poor hydrolytic stability.H ere we report our efforts to design and discover an ew series of tunable aminereactive electrophiles (TAREs) for selective and robust labeling of lysine.T he major challenges in developing selective probes for lysine are the high nucleophilicity of cysteines and poor hydrolytic stability.O ur work circumvents these challenges by au nique design of the TAREs that form stable adducts with lysine and on reaction with cysteine generate another reactive electrophiles for lysine.W eh ighlight that TAREs exhibit substantially high hydrolytic stability as compared to the activated esters and are non-cytotoxic thus have the potential to act as covalent ligands.W ea pplied these alternative TAREs for the intracellular labeling of proteins in different cell lines,and for the selective identification of lysines in the human proteome on aglobal scale.

An efficient strategy for synthesizing 3-(2-olefinbenzyl)-4H-chromen-4-one in two steps was developed. The first step is a cyclobenzylation reaction between (E)-3-(dimethylamino)-1-(2-hydroxyphenyl)prop-2-en-1-one and benzyl bromide to produce homoisoflavonoid. The second step involves intermolecular Pd-catalyzed π-chelating-assisted C-H bond olefination. Using the C-2/C-3 double bond of chromone, palladium-catalyzed aryl C-H bond activation can be functionalized to generate ortho-olefination derivatives in moderate to high yields.

Proteome profiling by activated esters identified > 9000 ligandable lysines but they are limited as covalent inhibitors due to poor hydrolytic stability.H ere we report our efforts to design and discover an ew series of tunable aminereactive electrophiles (TAREs) for selective and robust labeling of lysine.T he major challenges in developing selective probes for lysine are the high nucleophilicity of cysteines and poor hydrolytic stability.O ur work circumvents these challenges by au nique design of the TAREs that form stable adducts with lysine and on reaction with cysteine generate another reactive electrophiles for lysine.W eh ighlight that TAREs exhibit substantially high hydrolytic stability as compared to the activated esters and are non-cytotoxic thus have the potential to act as covalent ligands.W ea pplied these alternative TAREs for the intracellular labeling of proteins in different cell lines,and for the selective identification of lysines in the human proteome on aglobal scale.