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\n![\"polysulfide-1\"](\"https:\/\/www.peptide.co.jp\/public_html\/wp-content\/uploads\/2025\/12\/polysulfide-1.jpg\")
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What Are Supersulfides?<\/h3>\n
Supersulfides are molecules containing polysulfide chains formed by sulfur catenation, allowing for diverse reactivity. In biological systems, sulfur atoms are added to the thiol groups of cysteine and glutathione (GSH), forming hydropolysulfides such as CysSSH and GSSH [RS(S)n<\/sub>H], as well as polysulfides such as GSSSG [RS(S)n<\/sub>SR]. Supersulfides are extremely reactive and exert diverse physiological functions depending on their reaction partners. Under physiological conditions, supersulfides undergo repeated hydrolysis and reactions with nucleophiles and electrophiles, dynamically altering the number of sulfur atoms and generating a wide variety of molecular species8)<\/sup>. \u3000<\/p>\n \u3000 \u3000 \u3000 Supersulfides have become an increasingly important topic in life science research. Their high reactivity, dynamic chemical behavior, and diverse physiological functions are expected to greatly contribute to the elucidation of biological phenomena and disease mechanisms.
\nNumerous important findings on supersulfides have been reported by the research group of Professor Takaaki Akaike at Tohoku University. His group demonstrated that supersulfides are not mere metabolic byproducts but are actively synthesized by CARS2 (cysteinyl-tRNA synthetase), and that they play essential roles in antioxidant defense and signal transduction1,2)<\/sup>.
\nThese studies indicate that supersulfides are key regulators of oxidative stress, inflammation, and cellular signaling. Their roles are expected to contribute to the elucidation of biological phenomena, disease mechanisms, and the development of novel therapeutic strategies.
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\n![\"polysulfide-2\"](\"https:\/\/www.peptide.co.jp\/public_html\/wp-content\/uploads\/2025\/12\/polysulfide-2_en.png\")
\n\u3000<\/p>\nPhysiological Roles of Supersulfides<\/h3>\n
\n Potent antioxidant and anti-inflammatory activities<\/strong>
\n They efficiently react with reactive oxygen species (ROS), free radicals, peroxides, and metal ions, thereby exhibiting strong antioxidant and anti-inflammatory effects3,4)<\/sup>.
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\n Regulation of signal transduction<\/strong>
\n Supersulfides react with electrophiles such as 8-nitro-cGMP to reduce their reactivity, and also persulfidates protein cysteine residues, thereby contributing to the regulation of redox signaling, transcription, and metabolism1,7)<\/sup>.
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\n\u3000<\/p>\nChemical Properties of Supersulfides<\/h3>\n
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\n Dual nucleophilic and electrophilic reactivity<\/strong>
\nHydropolysulfides [RS(S)n<\/sub>H] normally behave as electrophiles; however, in the deprotonated persulfide anion state (RSS\u207b<\/sup>), they function as nucleophiles. This dual reactivity enables reactions with a wide range of chemical species.
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\nHigh reactivity at physiological pH<\/strong>
\nCatenation alters the electronic environment and lowers the pKa compared with the corresponding thiols. For example, while GSH has a pKa of approximately 8.9, GSSH has a significantly lower pKa of approximately 6.99)<\/sup>. Consequently, GSSH exists as a nucleophilic persulfide anion even under physiological pH, exhibiting high reactivity10)<\/sup>.
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\nDynamic sulfur transfer reactions<\/strong>
\nPolysulfides [RS(S)n<\/sub>SR] exhibit polarized sulfur\u2013sulfur bonds and are in hydrolytic equilibrium with water under physiological conditions. Through reactions with nucleophiles and electrophiles, sulfur atoms increase or decrease in number while undergoing transfer, rearrangement, elongation, and degradation, resulting in a cascade of supersulfide species.
\n![\"polysulfide-3\"](\"https:\/\/www.peptide.co.jp\/public_html\/wp-content\/uploads\/2025\/12\/polysulfide-3_en.png\")
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\nFig. Chemical properties of supersulfides
\nHydropolysulfides [RS(S)n<\/sub>H] exist in equilibrium between the protonated RSSH and persulfide anion RSS\u207b forms. Because GSSH has a pKa of approximately 6.9, it exists as a highly nucleophilic persulfide anion under physiological conditions. Polysulfides [RS(S)n<\/sub>SR] readily react with nucleophiles (including persulfides and water) and electrophiles due to charge polarization. As a result, supersulfides undergo chain reactions to generate diverse molecular species.
\n\u3000<\/p>\nFeatured Research Reagents<\/h3>\n
NAC Trisulfide (NAC-S1) \/ NAC Tetrasulfide (NAC-S2)<\/h4>\n
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\n![\"polysulfide-4\"](\"https:\/\/www.peptide.co.jp\/public_html\/wp-content\/uploads\/2025\/12\/polysulfide-4.jpg\")
\n\u3000<\/p>\nGSSSG\uff08Glutathione Trisulfide\uff09<\/h4>\n
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\n![\"polysulfide-5\"](\"https:\/\/www.peptide.co.jp\/public_html\/wp-content\/uploads\/2025\/12\/polysulfide-5.jpg\")
\n\u3000<\/p>\n\n\n
\n Code<\/th>\n Product Name<\/th>\n Quant<\/th>\n<\/tr>\n \n 3432-v<\/a><\/td>\n Glutathione Trisulfide<\/td>\n 5 mg<\/td>\n<\/tr>\n<\/tr>\n \n 3433-v<\/a><\/td>\n NAC Trisulfide<\/td>\n 5 mg<\/td>\n<\/tr>\n<\/tr>\n \n 3439<\/a><\/td>\n NAC Tetrasulfide<\/td>\n 5 mg<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
\n\u3000<\/p>\nThe Future\/Impact of Supersulfide Research<\/h3>\n
\nThe research reagents introduced here are powerful tools for efficiently analyzing the biological actions of supersulfides. We encourage their use in studies of oxidative stress, inflammation, and signal transduction.
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