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Targeted drug development and new tools, China to overcome the problem of peptides. Original technology daily


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Targeted drug development and new tools, China to overcome the problem of peptides.
Original technology daily
The 2018-04-08 16:03:37

Technology daily reporter sun yu-song reporter wu junhui.
Today, reporters learned from nankai university, the school element state key laboratory of organic chemistry professor Chen bow group have developed a powerful methods of synthesis of cyclic peptide compounds that plagued chemical industry for many years, "difficult polypeptide cyclization reaction" to realize the efficient and controllable. As an important breakthrough in the synthesis of cyclic peptides, the research also provides a novel design "tool" for the development of peptides. The results are published in the latest issue of the international journal nature chemistry.
According to introducing, compared with the traditional small molecule compounds, by a variety of amino acid unit in series of peptides compounds in building a larger molecular structure have unique advantages and potential, to known of cyclic peptide compounds including anti-tumor, anti-hiv, antibacterial, malaria, sleeping, inhibit platelet aggregation, immunosuppression and other aspects of biological activity. Both studies show that let the polypeptide chain "ring" can be in structural robustness, across cell membrane, metabolic stability significantly improved many ways, such as peptides into medicinal properties, and although in the past few decades of cyclic peptide synthesis chemistry has made considerable development, but still has great limitations, how to make these "big" "shape" for the ideal of peptide three-dimensional structure (cyclic peptide) and has good pharmacological properties and the great challenge.
Inspired by cyclic peptide the biosynthesis of natural products, Chen bow team of chain through metal catalytic peptides on the substrate was very inert alkyl hydrocarbon selective activation key, and with iodine and replace the aromatic amino acid side chains in intramolecular coupling to generate a variety of ring products. This method the palladium catalytic alkyl hydrocarbon activation key cleverly used in the synthesis of complex polypeptide, to "tame" many hard cyclization of linear peptide precursor, let them n-cyclohexylmaleimide "darling". Because the method USES the unconventional hydrocarbon key activation "synthetic strategy, method is simple and efficient, the substrate scope is wide, not only overcome the long plagued" peptide cyclization reaction substrate dependence, but also the efficient preparation has a unique "benzene racks" skeleton structure of three-dimensional cyclic peptide, to build different volume of cyclic peptide compounds provides a new universal way, also to find more good pilot drug activity, new type of cyclic peptide compounds promote targeting peptide drug development laid a solid foundation.