Nature chemistry: chemical method for rapid synthesis of eggs

Synthetic protein is an essential means in modern medicine and biological science As a supplementary means of expression of recombinant protein, chemical synthesis of protein has become a feasible method to obtain some target proteins, and has its unique advantages, such as high homogeneity, convenient addition of unnatural amino acids or post transcription modification, The enantiomers of proteins can also be prepared The natural chemical linkage (NCL) between thioester and N-terminal of cysteine published 20 years ago is a revolutionary progress in protein chemical synthesis, but it is not suitable for many synthesis targets So chemists have been looking for complementary and more general protein binding reactions with NCL methods Recently, a research team composed of Dr Ivano pustera and Professor Jeffery bode from the Federal Institute of technology in Zurich, Switzerland and the University of Nagoya, Japan, has successfully synthesized oxazetidine amino acids for the first time, which is a new linker tool that can rapidly synthesize proteins and has chemical selectivity Oxazetidine is a quaternary ring of hydroxylamine, which shows high reactivity due to its ring strain Bode's team has previously developed a Kaha (α - ketoacid hydroxamine) linkage reaction for the synthesis of a variety of proteins through the reaction of α - ketoacid and 5-membered hydroxylamine cycloprolines Then, this Kaha reaction system will lead to the introduction of unnatural homoserine residues at the junction The latest research results show that the binding reaction between the peptide containing oxazetidine and the Kaha of α - ketoacid can be carried out at a lower concentration and a mild temperature, which can produce proteins containing natural serine residues This kind of oxazetidine amino acid is the oxidation form of serine It has a relatively high abundance and can replace other amino acid residues without affecting the overall folding or function of the protein In the experiment, this reaction system was used to synthesize a calcium binding protein S100A4 with 100 amino acid residues This protein is usually difficult to synthesize by natural chemical linkage or other reactions to form amides However, the method of protein synthesis by oxazetidine amino acids and α - ketoacids has high reaction rate, good chemical selectivity and diversity, which is expected to become a powerful means of rapid chemical synthesis of useful proteins This research result was published in nature chemistry.