New synthesis method makes polypeptide "obedient" into a ring

Compared with the traditional small molecular compounds, the polypeptides which are composed of a variety of amino acid units in series have unique advantages and potential in building a larger molecular framework The known cyclopeptides have many biological activities, including anti-tumor, anti HIV, antibacterial, anti malaria, sleeping, platelet aggregation inhibition, immunosuppression and so on Previous studies have shown that the chain like polypeptide "ring" can significantly improve the drug-forming properties of polypeptide in many aspects, such as structural robustness, cell transmembrane, metabolic stability and so on Although the synthetic chemistry of cyclopeptides has made great progress in the past few decades, there are still great limitations How to make these "big" polypeptide molecules "shape" into ideal three-dimensional structure (cyclopeptides) and have good pharmacological properties is still a great challenge   A variety of cyclic products were formed by the selective activation of the originally inert alkyl hydrocarbon bonds on the chain peptide substrate and intramolecular coupling with the side chains of aromatic amino acids with iodine substitution In this method, palladium catalyzed activation of alkyl hydrocarbon bonds is cleverly used in the synthesis of complex polypeptides, which can "tame" many chain like polypeptide precursors that are difficult to form a ring and make them "obediently" close the ring Because of the unconventional strategy of "hydrocarbon bond activation" synthesis, the method is simple and efficient, and the substrate has a wide range of applications It not only overcomes the substrate dependence of "polypeptide cyclization" reaction for a long time, but also can efficiently prepare a three-dimensional cyclopeptide skeleton with a unique "benzene ring support frame" structure, which provides a new general way for the construction of cyclopeptide compounds with different volumes It also laid a solid foundation for the discovery of more new cyclic peptide compounds with good leading drug activity and the promotion of the research and development of targeted peptide drugs.