34223-44-4Relevant academic research and scientific papers
Characterization of the thiol/disulfide chemistry of neurohypophyseal peptide hormones by high-performance liquid chromatography
Yeo, Pauline L.,Rabenstein, Dallas L.
, p. 3061 - 3066 (1993)
Methodology is described for characterization of the kinetics and equilibria of thiol/disulfide interchange reactions of the disulfide bonds in the neurohypophyseal peptide hormones arginine vasopressin and oxytocin and the related peptides pressinoic acid and tocinoic acid. Thiol/disulfide interchange reaction mixtures are analyzed by reversed-phase high-performance liquid chromatography. The effect of mobile-phase composition and pH on the HPLC capacity factors for the native disulfide and reduced dithiol forms of each peptide was examined. In each case, the capacity factor decreases as the acetonitrile content of the mobile phase increases. For each disulfide/dithiol peptide pair, the capacity factor is larger for the dithiol form of the peptide, indicating that the hydrophobic side chains of the linear peptide are more accessible for interaction with the hydrophobic stationary phase. To illustrate application of the methodology, rate and equilibrium constants are reported for the thiol/disulfide interchange reactions of cysteine with arginine vasopressin at pH 7.0. Cysteine reacts with arginine vasopressin to form two mixed disulfides, which in turn react with another molecule of cysteine to give the dithiol form of arginine vasopressin and cystine. Rate and equilibrium constants were determined for each step by analysis of reaction mixtures by HPLC. The results are compared to rate and equilibrium constants for reaction of cysteine with oxidized glutathione.
Comparative reactivity of medicinal gold(i) compounds with the cyclic peptide vasopressin and its diselenide analogue
Alcoceba álvarez, Enrique,Cordeau, Emmanuelle,Enjalbal, Christine,Lamarche, Jeremy,Lobinski, Ryszard,Massai, Lara,Messori, Luigi,Ronga, Luisa
supporting information, p. 17487 - 17490 (2021/12/16)
The reactions of the medicinal gold(i) compound auranofin and its close analogues with vasopressin and the diselenide analogue were comparatively investigated by LC-electrospray MS/MS. Evidence is gained of the possible cleavage of the S-S and Se-Se bridg
IMPROVEMENTS IN SOLID PHASE PEPTIDE SYNTHESIS
-
Paragraph 0071-0076, (2017/08/01)
An improved method of deprotection in solid phase peptide synthesis is disclosed. In particular the deprotecting composition is added in high concentration and small volume to the mixture of the coupling solution, the growing peptide chain, and any excess activated acid from the preceding coupling cycle, and without any draining step between the coupling step of the previous cycle and the addition of the deprotection composition for the successive cycle. Thereafter, the ambient pressure in the vessel is reduced with a vacuum pull to remove the deprotecting composition without any draining step and without otherwise adversely affecting the remaining materials in the vessel or causing problems in subsequent steps in the SPPS cycle.
Converting disulfide bridges in native peptides to stable methylene thioacetals
Kourra,Cramer
, p. 7007 - 7012 (2016/11/23)
Disulfide bridges play a crucial role in defining and rigidifying the three-dimensional structure of peptides. However, disulfides are inherently unstable in reducing environments. Consequently, the development of strategies aiming to circumvent these deficiencies-ideally with little structural disturbance-are highly sought after. Herein, we report a simple protocol converting the disulfide bond of peptides into highly stable methylene thioacetal. The transformation occurs under mild, biocompatible conditions, enabling the conversion of unprotected native peptides into analogues with enhanced stability. The developed protocol is applicable to a range of peptides and selective in the presence of a multitude of potentially reactive functional groups. The thioacetal modification annihilates the reductive lability and increases the serum, pH and temperature stability of the important peptide hormone oxytocin. Moreover, it is shown that the biological activities for oxytocin are retained.
Thiol/disulfide exchange reactions of captopril and penicillamine with arginine vasopressin and oxytocin
Rabenstein, Dallas L.,Yeo, Pauline L.
, p. 109 - 118 (2007/10/02)
The kinetics and equilibria of the reaction of the thiol-containing drugs captopril (D-3-mercapto-2-methylpropanoyl-L-proline, CpSH) and penicillamine (β, β-dimethylcysteine, PSH) with the disulfide bonds of the neurohypophyseal peptide hormones arginine vasopressin (AVP) and oxytocin (OT) have been characterized. CpSH reacts with AVP and OT by thiol/disulfide interchange to form two peptide-CpSH mixed disulfides, which in turn react with another molecule of CpSH to form the reduced peptide and CpSSCp. Forward and reverse rate constants and the equilibrium constant are reported for both steps in the reaction of CpSH with AVP and OT at pH 7.00. The rate constant for the first step (k1) is much larger than that for the second step (k2). Also, once formed, the peptide-CpSH mixed disulfides rapidly undergo intramolecular thiol/disulfide interchange with reformation of the cyclic peptide and CpSH. PSH reacts with AVP and OT by the same two-step reaction sequence; however, the rate of the second step is very slow due to steric hindrance from the methyl groups of PSH and the PSH moiety of the peptide-PSH mixed disulfides. Using rate constants determined in this study and PSH levels in the plasma of patients on PSH therapy, it is predicted that in vivo reduction of the disulfide bonds of AVP and OT by PSH and CpSH has little effect on the plasma half-lives of AVP or OT.
Kinetics and Equilibria of the Formation and Reduction of the Disulfide Bonds in Arginine-Vasopressin and Oxytocin by Thiol/Disulfide Interchange with Glutathione and Cysteine
Rabenstein, Dallas L.,Yeo, Pauline L.
, p. 4223 - 4229 (2007/10/02)
Rate and equilibrium constants are reported for reduction of the disulfide bonds in the neurohypophyseal peptide hormones oxytocin (OT) and arginine-vasopressin (AVP) by thiol/disulfide interchange with glutathione (GSH) and cysteine (CySH) and for formation of the disulfide bonds by thiol/disulfide interchange with oxidized glutathione (GSSG) and cystine (CySSCy).The reactions take place in two steps.In the first step of the reduction reactions, AVP and OT react with GSH and CySH to form peptide-GSH and peptide-CySH mixed disulfides, which in turn react with another molecule of GSH or CySH to give the reduced dithiol form of the peptide and GSSG or CySSCy.Analysis of the forward and reverse rate constants indicates that which step is rate determining depends on the concentration of GSH or CySH.At physiological concentrations of GSH and CySH, intramolecular thiol/disulfide interchange in the mixed disulfides to reform the native disulfide bonds is faster than reaction with another molecule of GSH or CySH, even though intramolecular thiol/disulfide interchange involves closure of 20-membered rings.Rate constants for reaction of GSH and CySH with the disulfide bonds of AVP and OT are 1-2 orders of magnitude larger than for reaction with disulfide bonds formed by two cysteine-containing peptides, which suggests that the disulfide bonds in the neurohypophyseal peptide hormones are strained.Equilibrium constants are also reported for reaction of GSH with the hexapeptide analogs of AVP and OT, pressinoic acid (PA), and tocinoic acid (TA).A reduction potential of -0.216 V was calculated for the disulfide bonds of OT and TA from the thiol/disulfide interchange equilibrium constants.Reduction potentials of -0.229 V and -0.227 V were calculated for the disulfide bonds in AVP and PA, respectively.The similarity of the reduction potentials for OT and TA and for AVP and PA indicates that the acyclic tripeptide tails of OT and AVP have little affect on the redox properties of their disulfide bonds.
