Enzymic catalysts of thiol:disulfide oxidoreduction contain two cysteine residues in their active sites. Another common residue is an aspartate (or glutamate), the role of which has been unclear. Escherichia coli thioredoxin (Trx) is the best characterized thiol:disulfide oxidoreductase, and in Trx these three active-site residues are Cys32, Cys35, and Asp26. Structural analyses had indicated t...

Divercin V41 (DV41) is a class IIa bacteriocin produced by Carnobacterium divergens V41. This antilisterial peptide is homologous to pediocin PA-1 and contains two disulfide bonds. To establish the structure-activity relationships of this specific family of bacteriocin, chemical modifications and enzymatic hydrolysis were performed on DV41. Alteration of the net charge of this cationic bacterio...

Protein disulfide bonds link pairs of cysteine sulfur atoms and are either structural or functional motifs. The allosteric disulfides control the function of the protein in which they reside when cleaved or formed. Here, we identify potential allosteric disulfides in all Protein Data Bank X-ray structures from bonds that are present in some molecules of a protein crystal but absent in others, o...

Conditions leading to cleavage of all of the disulfide bridges in ribonuclease and several other proteins (0.32 M Z-mercaptoethanol in 8 M urea) caused in papain only partial reduction of the disulfide bonds. Electrophoretic studies indicated that alkylation of the partially reduced derivative yielded a unique molecular species (3-RCM papain) in which one specific disulfide bond had been split,...

Deubiquitinating enzymes (DUBs) catalyze the cleavage of ubiquitin from target proteins. Ubiquitin is post-translationally attached to proteins and serves as an important regulatory signal for key cellular processes. In this study, novel activity-based probes to study DUBs were synthesized that comprise a ubiquitin moiety and a novel disulfide warhead at the C-terminus. These reagents can bind ...

Disulfide bonds provide a bioactivatable connection with applications in imaging and therapy. The circulation stability and intracellular release of disulfides are problematically coupled in that increasing stability causes a corresponding decrease in cleavage and payload release. However, an antibody offers the potential for a reversible stabilization. We examined this by attaching a small mol...

Reducible heparin nanogels cross-linked with disulfide linkages were developed for efficient cellular uptake of therapeutic heparin to induce apoptotic cell death. The heparin nanogels were synthesized by forming nanocomplexes between thiolated heparin and poly(ethylene glycol) in a selected organic solvent, and subsequently producing intermolecular disulfide bonds between thiolated heparin mol...

A novel fluorescence probe capable of assessing the cytoplasmic entry of siderophore-based conjugates was synthesized and evaluated by photochemical characterization and cell-based assays. The specific responsiveness to the cytoplasmic entry of the probe was implemented by adopting a disulfide linker, whose cleavage under the reducing conditions of the cytoplasm induced the display of a distinc...

Reductive S-S bond cleavage of a disulfide precursor obtained from a pyridine-catalyzed Peterson-type reaction starting from camphorpyrazole , thionyl chloride and 2-methyl-2-(methyldithio)propionaldehyde yields 2,2'-bis(camphorpyrazol-1-yl)-2-methylpropane-2-thiol (HSiprbpm3cam, ); the first zinc complexes bearing this ligand exhibit kappa3 coordination of the ligand.