Abstract
Some peptide-based drugs, including oxytocin, vasopressin, ziconotide, pramlintide, nesiritide, and octreotide, contain one intramolecular disulfide bond. A novel and reusable monodispersed silica nanosphere-supported Pt(IV) complex (SiO2@TPEA@Pt(IV)); TPEA: N-[3-(trimethoxysilyl)propyl]ethylenediamine) was synthesized via a four-step procedure and was used for the formation of intramolecular disulfide bonds in peptides. Transmission electron microscopy (TEM) and chemical mapping results for the Pt(II) intermediates and for SiO2@TPEA@Pt(IV) show that the silica nanospheres possess a monodisperse spherical structure and contain uniformly-distributed Si, O, C, N, Cl, and Pt. The valence state of Pt on the silica nanospheres was characterized by X-ray photoelectron spectroscopy (XPS). The Pt(IV) loaded on SiO2@TPEA@Pt(IV) was 0.15 mmol/g, as determined by UV-VIS spectrometry. The formation of intramolecular disulfides in six dithiol-containing peptides of variable lengths by the use of SiO2@TPEA@Pt(IV) was investigated, and the relative oxidation yields were determined by high-performance liquid chromatography (HPLC). In addition, peptide 1 (Ac-CPFC-NH2) 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.
Highlights
A large fraction of the peptide-based drugs available on the market, including oxytocin, vasopressin, ziconotide, pramlintide, nesiritide, and octreotide, contain one or multiple intramolecular disulfide bonds
Trans-[PtCl2(en)2]2+ was found to be a highly selective and efficient reagent for the rapid and quantitative formation of disulfide bonds in peptides [11]; no side reactions occurred on the side chains of tryptophan, tyrosine, and methionine, and no dimers formed, though an intermolecular disulfide link was observed with the Pt(IV) complex [11]
The relative oxidation yield is defined as SA/SB, where SA refers to the peak area corresponding to oxidized peptide 1 generated by the oxidation of SiO2@TPEA@Pt(IV) (Figure 3b), and SB pertains to the peak area of oxidized peptide 1 generated by trans-[PtCl2(en)2]2+ (Figure 3c)
Summary
A large fraction of the peptide-based drugs available on the market, including oxytocin, vasopressin, ziconotide, pramlintide, nesiritide, and octreotide, contain one or multiple intramolecular disulfide bonds. 2 (en)2 ] , dihydroxyselenolane oxide (DHX ), and N-chlorosuccinimide (NCS) have and utilized for and the formation disulfide bonds in peptides [10,11,12,13,14,15,16,17,18]. It has been found that at least a ten times (Oxyfold reagent), and ChemMatrix-supported NCS have been developed [19,20,21,22].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
