Method Studies On Cyclic Peptide Synthesis Via Natural Chemical Ligation And Peptide N-terminus Cysteine Protection

As the executor of life,proteins play a very important role in our human body,which is closely connected with structure and growth of human body,development and disease.The three sources of protein are biological expression,chemical semisynthesis and chemical total synthesis,respectively.Chemical synthesis of peptide plays a significant role in the total synthesis of functional peptides,modified polypeptide as well as modified protein.Native chemical ligation method is widely used in the connection of longer peptide sequence,for which the selection of the connection site is in cysteine.The mechanism of the reaction is the C-terminal thioester of a peptide exchanged with the N-terminal Cys,after which the peptides automatically formed natural peptide bond by moved from S to N.Peptides,proteins and its derivatives have diversified structure and its own biological functions.However,its stability in the body is not good and its half-life is short,various modification of polypeptide structure is in need.Therefore,cyclization of peptides is chosen to change the problem of stability and the short half-life.In addition,some cyclic peptide structure such as RGD cyclic peptide has better tumor targeted effect,also become one of the drugs targeting transport strategy.In this paper,natural chemical connection methods of peptide side chain is using to design and synthesize a series of novel RGD cyclic peptides,including branched chain peptide,branched-chain monocyclic peptide,branched-chain dicyclic peptide and so on.Moreover,a now cyclic peptides has been generated,this series of peptide links were tagged by azide for easily biological activity test in future.This method can promote the development of cyclic peptides application in medicine and improve the synthetic method of peptide side chain with the advantage of mild reaction conditions simplified operational procedure and the raw materials easy to get.Another work of this paper involves the development of new protection strategy of N-terminal cysteine of peptide.Peptide substrate which is identified by specific proteolytic enzyme is used as N-terminal cysteine protection base,after the natural chemistry peptide connection the corresponding hydrolytic enzyme is adopted to remove protection peptide sequence and the N-terminal cysteine exposed to further polypeptide connection.The advantages of this method are not only the enzyme compatible with peptide connection reaction system,but also the mild reaction conditions,simple principle,simple operation,obtained the periodic achievements by the optimization of system.