A new synthesis method of Nankai University makes polypeptide "obedient" into a ring

The reporter recently learned from Nankai University that Professor Chen Gong, the State Key Laboratory of elemental organic chemistry of Nankai University, has developed a chemical synthesis method of strong cyclic polypeptide compounds, which has made the "high difficulty polypeptide cyclization" reaction that has puzzled the chemical industry for many years efficient and controllable As an important breakthrough in the field of cyclopeptide molecular synthesis chemistry, this research also provides a novel design tool for peptide drug development Relevant research results are published in the latest issue of nature chemistry According to reports, compared with the traditional small molecular compounds, the polypeptide compounds formed by a series of amino acid units have unique advantages and potential in building a larger molecular framework The known cyclopeptide compounds have many biological activities, including anti-tumor, anti HIV, anti bacteria, anti malaria, sleeping, inhibiting platelet aggregation, 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 Inspired by the natural product biosynthesis of cyclopeptide, Chen Gong's team selectively activated the originally inert alkyl hydrocarbon bond on the chain peptide substrate through metal catalysis, and carried out intramolecular coupling with the aromatic amino acid side chain with iodine substitution to generate various ring products 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.