Preparation Of Novel Light-Driven Peptide Synthesizer

Peptides are compounds formed by amino acids being linked together in the form of peptide bonds,and are widely used in biomedical science,material science,nutrition and health care,chemistry and chemical engineering.The chemical synthesis method of peptide includes solid phase synthesis method and liquid phase synthesis method,natural chemical connection method belongs to one of the liquid phase synthesis method,the method is a thiol group in the cysteine side chain group to exchange esters and then molecular acyl group transfer to form peptide bond reaction.The method is a peptide synthesis method with mild reaction conditions,high selectivity and good reactivity.However,the limitation of this method is that cysteine must be involved,which greatly limits its application range.Based on the principle of natural chemical ligation method,this project designed and synthesized a molecular machine based on photoisomerization to synthesize peptides,the light-driven peptide synthesizer,which is used to overcome the limitations of cysteine participation required by the above natural chemical ligation methods and improve the applicability of its substrate amino acids.In this project,1-indanone is used as a raw material to synthesize a photoisomerized molecular machine with carbon-carbon double bonds in 15 steps.The molecular machine in the double bond at each end of a five-membered carbon ring connected to thiophenol,through the construction of a mercapto group,lifted the restriction that the cysteine side chain mercapto group must participate in the reaction;under the conditions of light or heating can occur cis-trans isomer reaction,under the condition of trans configuration,the thiol group on the thiophenol under certain conditions can be successively formed with amino acids to form thioesters,and then under certain light,the molecular machine changes from trans to cis,Narrowing the spatial distance between the two molecules of amino acids and thus promoting the formation of peptide bonds by an acyl transfer reaction similar to the natural chemical linkage method.Using this method,the dipeptide formed by valine and alanine was successfully synthesized,which greatly improved the application of natural chemical ligation method.The resulting intermediates and final products were characterized and attributed by ~1H-NMR.By synthesizing valine-alanine dipeptide,the feasibility of the polypeptide synthesizer synthesis of peptides is proved,the synthesizer can also be selectively removed after the peptide synthesis task is completed,and can be reused after separation,in addition,theoretically the synthesizer can be applied to the peptide synthesis of any amino acid substrate,so this greatly expands the scope of use of natural chemical ligation method.