Oxidative Synthesis Of Intramolecular Disulfide Bonds In Peptides By Pt(?) Complex And Solid Supported Pt(?) Complex

At present,peptide drugs have been used for the treatment of various diseasesin,such as anti-tumor drugs,cardiovascular drugs and other fields.Disulfide bonds exist in many proteins and polypeptides,which are mainly used to maintain their structural stability.And disulfide bonds determine the structural stability and function of peptide molecules.Therefore,the synthesis of disulfide bonds is a very important part for the synthesis of disulfide bond in peptides.There are many methods for synthesizing intramolecular disulfide bonds in peptides,among which tetravalent platinum complexes are used as important reagents for exploring synthesis of intramolecular disulfide bond in peptides.In our work,studies on oxidized synthetic of intramolecular disulfide bonds in peptides by[Pt?en?₂Br₂]Cl₂ were developed,and relative oxidation yield was determined by HPLC.The results showed that[Pt?en?₂Br₂]Cl₂ can rapidly oxidize and synthesize intramolecular disulfide bonds without side reactions to methionine,tryptophan,and tyrosine residues.And[Pt?en?₂Br₂]Cl₂ is suitable for acidic media.Thus[Pt?en?₂Br₂]Cl₂ is an oxidant with high oxidation yield that synthesizes intramolecular disulfide bonds quickly and efficiently.And its reaction mechanism has been studied and summarized in our work.Solid-phase loaded reagents are stable,and can be separate or recycled easily.Therefore,a polymer oxidant loaded with a Pt???complex was synthesized,namely TentaGel-Pt???microspheres.It is used to oxidative synthesis intramolecular disulfide bonds in peptides.TentaGel-Pt???was characterized by SEM,EDS and ICP-MS.The loading of Pt???was determined using a UV-vis spectrophotometer.Formation of intramolecular disulfides in eleven dithiol-containing peptides of variable lengths by use of TentaGel-Pt???was investigated,and the relative oxidation yields were determined by HPLC.The results showed that TentaGel-Pt???can rapidly oxidize and synthesize intramolecular disulfide bonds without side reactions to methionine,tryptophan,and tyrosine residues.And TentaGel-Pt???is an oxidant with high oxidation yield that synthesizes intramolecular disulfide bonds quickly and efficiently.In addition,TentaGel-Pt???is stable,and can be separate or recycled easily.The reusability of TentaGel-Pt???microspheres was studied by using the reduced peptide iRGD as an example.The results showed that TentaGel-Pt???can be reused at least 20 times without significant decrease of oxidation yield.