17912-60-6Relevant articles and documents
Palladium-Mediated Direct Disulfide Bond Formation in Proteins Containing S-Acetamidomethyl-cysteine under Aqueous Conditions
Laps, Shay,Sun, Hao,Kamnesky, Guy,Brik, Ashraf
, p. 5729 - 5733 (2019)
One of the applied synthetic strategies for correct disulfide bond formation relies on the use of orthogonal Cys protecting groups. This approach requires purification before and after the deprotection steps, which prolongs the entire synthetic process and lowers the yield of the reaction. A major challenge in using this approach is to be able to apply one-pot synthesis under mild conditions and aqueous media. In this study, we report the development of an approach for rapid disulfide bond formation by employing palladium chemistry and S-acetamidomethyl-cysteine [Cys(Acm)]. Oxidation of Cys(Acm) to the corresponding disulfide bond is achieved within minutes in a one-pot operation by applying palladium and diethyldithiocarbamate. The utility of this reaction was demonstrated by the synthesis of the peptide oxytocin and the first total chemical synthesis of the protein thioredoxin-1. Our investigation revealed a critical role of the Acm protecting group in the disulfide bond formation, apparently due to the generation of a disulfiram in the reaction pathway, which significantly assists the oxidation step.
Occurrence and Minimization of Cysteine Racemization during Stepwise Solid-Phase Peptide Synthesis
Han, Yongxin,Albericio, Fernando,Barany, George
, p. 4307 - 4312 (1997)
Contrary to the conventional wisdom of the peptide synthesis field, N,S-protected derivatives of cysteine can undergo substantial levels of racemization with widely-used reagents and protocols for stepwise incorporation. A systematic study of this problem
Bioconjugation through Mesitylene Thiol Alkylation
Ramos-Tomillero, Iván,Perez-Chacon, Gema,Somovilla-Crespo, Beatriz,Sanchez-Madrid, Francisco,Domínguez, Juan Manuel,Cuevas, Carmen,Zapata, Juan Manuel,Rodríguez, Hortensia,Albericio, Fernando
, p. 1199 - 1208 (2018)
The design and generation of complex multifunctional macromolecular structures by bioconjugation is a hot topic due to increasing interest in conjugates with therapeutic applications. In this regard, the development of efficient, selective, and safe conjugation methods is a major objective. In this report, we describe the use of the bis(bromomethyl)benzene scaffold as a linker for bioconjugation with special emphasis on antibody conjugation. We first performed the monothioalkylation of 1,3,5-tris(bromomethyl)benzene, which rendered the reactive dibromotrimethylbenzyl derivatives to be used in thiol bis-alkylation. Next, we introduced into the linker either a bis(Cys)-containing peptide or anti-CD4 and -CD13 monoclonal antibodies, previously subjected to partial reduction of disulfide bonds. Mass spectrometry, UV-vis spectra, and SDS-PAGE experiments revealed that this bis-alkylating agent for bioconjugation preserved both antibody integrity and antibody-antigen binding affinity, as assessed by flow cytometry. Taken together, our results show that the mesitylene scaffold is a suitable linker for thiol-based bioconjugation reactions. This linker could be applicable in the near future for the preparation of antibody drug conjugates.
Detection of Thiol Functionality and Disulfide Bond Formation by Polyoxometalate
Konno, Hiroyuki,Yasumiishi, Haruto,Aoki, Reika,Nitanai, Ikumi,Yano, Shigekazu
supporting information, p. 745 - 749 (2020/11/10)
The detection of thiol functionality and intramolecular disulfide bond formation of peptides using the α-Keggin type polyoxometalate molybdenum-oxygen cluster (H3PMo12O40·nH2O) is described. Our method entails the addition of this polyoxometalate to solutions of thiol, whereupon the color of the solution changes from colorless to deep blue. Reduction of the polyoxometalate from Mo(VI) to Mo(V) occurs with concomitant oxidation of the thiol functionality, to form disulfide bonds. To exemplify the utility this phenomenon, we accomplished the oxidation of glutathione, reduced linear oxytocin, bactenecin, and α-conotoxin SI; all of which proceeded smoothly and in good conversion in 24 h to less and were accomplished by a change in the color of the reaction solutions.
Selective disulfidation reagent using nitrogen-containing compound and method for producing disulfide-containing compound
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Page/Page column 26, (2020/12/02)
The present invention provides a means capable of selectively introducing a disulfide bond with respect to two free thiol groups located in a molecule of an organic compound such as a peptide, or the like, in a short time by a simple treatment and also by a chemically stable method. A nitrogen-containing compound represented by Chemical Formula 1 below or a salt thereof: The symbols shown in Chemical Formula 1 are the same as defined in the specification.
