Synthesis Of Solid Supported Pt(Ⅳ) Complex And Oxidative Synthesis Of Disulfide Bonds In Peptides

In recent years,the peptide drugs with good stability,strong specificity,weak immunogenicity get rapid development.Among them,a large part of the peptide drugs containing intramolecular disulfide bond,which is of great significance in both the structure and function characteristics.The efficient synthesis of intramolecular disulfide bond is becoming a hot spot in recent years.There are a variety of methods for the synthesis of intramolecular disulfide bonds,including homogeneous oxidation and solid phase oxidation.With the extensive study of Pt（Ⅳ）complexes as anticancer prodrugs,it has been found that Pt（Ⅳ）complexes can oxidize thiol groups to form intermolecular or intramolecular disulfide bonds.But platinum is expensive and difficult to recycle.Nano-silica has become research hot spots of a variety of cross-field with its large surface area,high chemical activity and the property of easy to be modified.In this paper,a novel and reusable monodispersed nanosphere-supported Pt（Ⅳ）oxidant（SiO₂@TPEA@Pt（Ⅳ））was successfully synthesized via a four-step procedure and characterized using fourier transform infrared spectroscopy（FT-IR）,transmission electron microscopy（TEM）,elemental analysis,inductively coupled plasma mass spectrometry（ICP-MS）,X-ray photoelectron spectroscopy（XPS）,ultraviolet-visible spectroscopy（Uv-vis）.The formation of intramolecular disulfides in Ac-CPFC-NH2（peptide 1）and other dithiol-containing peptides of variable lengths by the use of Si O₂@TPEA@Pt（Ⅳ）was investigated,and the relative oxidation yields were determined by high-performance liquid chromatography（HPLC）.In addition,the reactions between peptide with SiO₂ after oxidized,SiO₂@TPEA and SiO₂@TPEA@Pt（II）were studied to conform no oxidation reactions.Peptide 1 was utilized to study the reusability of SiO₂@TPEA@Pt（Ⅳ）.No significant decrease in the relative oxidation yield was observed after ten reaction cycles.Moreover,the structure of SiO₂@TPEA@Pt（Ⅳ）after being used for ten cycles was determined to be similar to its initial one,demonstrating the cycling stability of the complex.The application of the SiO₂@TPEA@Pt（Ⅳ）oxidant has significance for the synthesis of intramolecular disulfides.