Peptide synthesis method

Many kinds of life processes are regulated by the interaction between proteins For example, virus self-assembly, cell growth, division, differentiation and other processes In general, the protein-protein interaction interface is too large, which makes it difficult for small molecule drugs to target them, so as to block the interaction effectively and specifically, and show good therapeutic effect Because it is difficult for protein drugs to pass through the cell membrane smoothly, so they can not achieve the effect of directly targeting the intracellular interaction Therefore, researchers began to seek a new drug molecule that can not only enter the cell membrane but also specifically target the protein-protein interaction, which can overcome the shortcomings of the two drugs It has been shown that peptides with α - helix structure and rich positive charge can pass through the cell membrane However, once separated from the mother, it can not maintain its original secondary structure, and the instability of conformation leads to the weakening of its binding with protein, while the common linear peptide can not pass through the cell membrane and is easy to be hydrolyzed After continuous attempts, verdine and others have developed a new structure of peptide, which is called stapling peptide It is a kind of peptide with a-helix structure of all carbon scaffold, and all carbon scaffold stabilizes α- The spiral structure enhances the interaction between peptide and protein, and the binding peptide can pass through the cell membrane and is not easy to be hydrolyzed Compared with the previous small molecule drugs and protein drugs, it has higher pharmacological activity The difference between the synthesis of stapling peptide and the synthesis of common peptide is that two unnatural amino acids containing α - methyl and α - alkenyl are introduced into the solid-phase synthesis of peptide chain, and then the olefin metathesis reaction between the two unnatural amino acids cyclizes to form a stable all carbon scaffold with α - helix structure, and then the stapling peptide is synthesized The above figure shows the general structure of two different configurations of unnatural amino acids containing α - methyl and α - alkenyl groups This type of amino acid synthesis method is generally: the general synthesis route of stapling peptide is: Guopeptide biology always adheres to the business philosophy of customer first Through long-term experiment accumulation and continuous optimization of synthesis conditions and purification process, it has possessed mature synthesis process of stapling peptides, the ability to provide high-quality stapling peptides to the world, and can fully meet various R & D needs of customers Successful case: synthesis of the following structural stapling peptide HPLC analysis: MS analysis: