The Study Of Bioconjugation Between Dehydroalanine And Sulfinic Acid

The natural modified proteins have been unable to meet the research needs of researches in the field of chemical biology.Scientists also need non-naturally modified proteins that are not available with specific functional and traditional gene expression techniques.As a result,researchers have evolved organic chemical reactions from test tubes into complex organisms.At present,it has been reported in the literature that the side chain cysteine residue of the protein can be "chemically mutated" to dehydroalanine(Dha),and the protein could be directly modified by the addition reaction with the small molecule compound.The Michael addition reaction of dehydroalanine with amino or thiol has been successfully applied in protein modification.According to the soft and hard acid-base theory,the sodium sulfinate are more susceptible to the conjugate addition reaction with the dehydroalanine than the amino group.Based on the above reports,we investigated the model reaction between sodium sulfinate and dehydroalanine,and found that the reaction can performed faster in the simulated physiological environment without side reactions,and with a high pH tolerance of the reaction product,and the reaction is also catalyst-free.We also performed the bioconjugation between three common proteins and sodium benzyl sulfinate,and it did not destroy the disulfide bonds inside the protein.By using the conjugate addition reaction between sodium sulfinate and protein dehydroalanine,we can simulate the oxidative modification of protein sulfur-containing amino acid residues,and further study its physiological and pathological functions for the diagnosis treatment of related diseases and drug development.