Progress in peptide synthesis and nuclear magnetic resonance structure analysis after disulfide substitution

Recently, Tian Changlin research group of strong magnetic field science center of Hefei Institute of material science, Chinese Academy of Sciences and Liu Lei research group of Tsinghua University have carried out the research on the synthesis of toxin polypeptide based on the solid-phase method of replacing disulfide bond cysteine with two amino acids and the structural analysis of its application by NMR The stable conformation synthesis of toxin polypeptide containing many disulfide bonds has been realized, and in the NMR junction The importance of long-range disulfide bond to the conformational stability of toxin peptide was determined on the basis of structure analysis Toxin polypeptides can effectively inhibit the growth of bacteria, fungi or eukaryotic cells, especially a variety of toxin polypeptides have been found to effectively inhibit or enhance the selectivity or gating properties of ion channel proteins However, these toxin peptides contain many pairs of disulfide bonds composed of cysteine, which makes it difficult to obtain stable conformation of toxin peptides prepared by genetic engineering or chemical synthesis due to disulfide bond mismatch To solve this key problem, cys-c-s-cys, or cys-c-cys double amino acids were used to simulate and replace cys-s-s-cys, which formed disulfide bond, and high yield toxin peptide synthesis was obtained, effectively avoiding disulfide bond mismatch In this study, the chemical shifts of 9 different peptides were analyzed by liquid NMR, and the three-dimensional structures of 4 peptides were obtained The analysis of NMR data of different peptides shows that the substitution of long-range disulfide bond plays a key role in the conformational stability of toxin peptides The related research results were published online on June 26 in the Journal of Angewandte Chemie International Edition (DOI: 10.1002 / anie 201302197) with the title of diaminodiacid based solid-phase synthesis of peptides after disulfide bond substitution (solid-phase synthesis of peptides based on double amino acids) Yao, postdoctoral students Cui Hongkui and Guo ye from Tsinghua University are the co first authors of the paper Dr Wu Fangming from the center for strong magnetic field science of the Chinese Academy of Sciences also participated in the research.