Peptide Knowledge Center

Classification and research of stapled peptides

At present, staple peptides can be divided into two categories according to the type of bridging structure (stapling bridge). Heteroatom-containing Chain Stapling Bridge Stapling Peptides Using Heteroatoms as Linking Reaction Centers

Protein-protein interactions (PPIs) play a decisive role in regulating the life activities of the body and are the key mechanisms of many signaling pathways in the body, many of which are potential drug targets. Exploring methods to effectively regulate protein-protein interactions will be of great benefit to physiological and pharmaceutical research. The vast majority of protein-protein interactions occur in relatively large and shallow interaction surfaces, and it is difficult for small molecules to form effective binding or regulation. The α-helical peptide in the folded subdomain supported by the secondary structure of the polypeptide in the protein-protein interaction is separately extracted and constructed by chemical synthesis. It is possible to obtain active polypeptides that selectively act on the target protein. drug lead. However, After leaving the overall structure of the protein, the polypeptide fragment will not be able to stably form the secondary structure required for binding, but is prone to form a random coiled conformation, which leads to a decrease in binding activity, and is more susceptible to degradation by peptidase, so it cannot be directly formulated into a drug.

The application of an all-carbon backbone to form a side chain cyclization structure to modify the peptide to stabilize the active conformation of the α-helical peptide, that is, the stapled peptide, has become the most direct and effective method to overcome this defect. This method not only improves its original protein-binding activity, but also has high metabolic stability and cell membrane permeability. Based on these significant advantages, stapled peptides have become an important way of structural modification of active peptides, and will also lead to the formation of more new peptide drugs targeting protein-protein interactions. This article will focus on

This review summarizes and discusses the research progress on the synthesis of stapled peptides by chemical means and their pharmacological activities.