66513-06-2Relevant articles and documents
Discovery of a highly selective and efficient reagent for formation of intramolecular disulfide bonds in peptides
Shi, Tiesheng,Rabenstein, Dallas L.
, p. 6809 - 6815 (2000)
We have discovered that trans-[Pt(en)2Cl2]2+ (en = ethylenediamine) is a highly selective and efficient reagent for the quantitative formation of intramolecular disulfide bonds in peptides. A series of 14 dithiol peptides which form disulfide-containing rings ranging in size from 14 to 53 atoms were used to characterize the reagent. The dithiol peptides are cleanly and rapidly converted to their disulfide forms by a slight excess of the platinum complex under mild reaction conditions (slightly acidic and neutral media). For all the dithiol peptides studied, including a penicillamine-derived peptide, the oxidation yields range from 97% to 100%. No side reactions were observed, including no oxidation of the methionine side chain. The reaction kinetics for oxidation of reduced pressinoic acid were found to be second order overall: rate = k'[Pt(IV)][dithiol peptide], where k' is a pH-dependent second-order rate constant. Values of 0.60 ± 0.01, 3.5 ± 0.2, and 22 ± 1 M-1 s-1 were determined for k' at pH 3.0, 4.0, and 5.0, respectively (25 °C and 0.45 M ionic strength). A reaction mechanism for oxidation of dithiol peptides by [Pt(en)2Cl2]2+ is proposed. [Pt(en)2Cl2]2+ and its reduction product [Pt(en)2]2+ are essentially substitution inert under the conditions used for disulfide formation, they are nontoxic, and they are readily separated from peptides by HPLC. The characteristics of [Pt(en)2Cl2]2+ and its reaction properties with dithiol peptides suggest that [Pt(en)2Cl2]2+ is a universal reagent for the rapid and quantitative formation of intramolecular disulfide bonds in peptides.
Trans-Dichlorotetracyanoplatinate(IV) as a Reagent for the Rapid and Quantitative Formation of Intramolecular Disulfide Bonds in Peptides
Shi, Tiesheng,Rabenstein, Dallas L.
, p. 4590 - 4595 (2007/10/03)
Oxidation of cysteine thiol groups by trans-dichlorotetracyanoplatinate(IV) to form intramolecular peptide disulfide bonds has been studied for a series of dithiol peptides ranging from 4 to 15 amino acid residues in length. The dithiol peptides are rapidly and quantitatively transformed to their intramolecular disulfide forms by a slight excess of [Pt(CN)4Cl2]2-, as shown by HPLC. Quantitative analyses by HPLC and by spectrophotometric titration confirm a [Pt(IV)]:[dithiol peptide] stoichiometry of 1:1. Under the low pH conditions used, oxidation to form a 38-membered ring in the case of reduced somatostatin is as rapid as that to form much smaller rings, suggesting that ring closure is not the rate-determining step. The oxidation rates increase as the pH is increased. Time-resolved spectra show two isosbestic points, indicating that no peptide-platinum intermediates accumulate to a significant amount. A reaction mechanism similar to that for reduction of [Pt(CN)4Cl2]2- by monothiols is proposed. [Pt(CN)4Cl2]2- is a mild oxidant and essentially substitution inert; its reduction product, [Pt(CN)4Cl2]2-, is stable, has no redox chemistry with peptides, and does not form complexes with peptides. Moreover, [Pt(CN)4Cl2]2- and [Pt(CN)4Cl2]2- are nontoxic and readily separable from peptides by HPLC, and the cost of the Pt(IV) complex is negligible compared with that of peptides. The only unwanted side reaction observed with [Pt(CN)4Cl2]2- is oxidation of the sulfur of methionine to the sulfoxide form. These characteristics and the results of this study suggest that [Pt(CN)4Cl2]2- is an excellent reagent for the formation of intramolecular peptide disulfide bonds.
A MODIFIED BENZHYDRYLAMINE - A USEFUL HANDLE REAGENT FOR Fmoc BASED SOLID PHASE SYNTHESIS OF PEPTIDE AMIDES
Funakoshi, Susumu,Murayama, Eigoro,Guo, Lili,Fujii, Nobutaka,Yajima, Haruaki
, p. 2791 - 2800 (2007/10/02)
Usefulness of a dimethoxybenzhydrylamine derivative, 3-(3-(Fmoc-amino-4-methoxyphenylmethyl)-4-methoxyphenyl)propionic acid, for Fmoc-based solid phase synthesis of peptide amides was demonstrated by preparation of three biologically active peptide amides, i.e. tetragastrin, neuromedin B and vasopressin. 1M trimethylsilyl bromide-thioanisole (molar ration 1 : 1) in trifluoroacetic acid was recommended as a deprotecting reagent for releasing the peptide amides from the resin.
