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Title: 9-Fluorenylmethyl (Fm) Disulfides: Biomimetic Precursors for Persulfides

Journal Article · · Organic Letters
 [1];  [1];  [2];  [3];  [1];  [3];  [2];  [1]
  1. Department of Chemistry, Washington State University, Pullman, Washington 99164, United States
  2. Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington 99352, United States
  3. Tissue Imaging and Proteomics Laboratory, Washington State University, Pullman, Washington 99164, United States
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Protein S-sulfhydration has been recognized as an important post-translational modification that regulates H2S signals. However, the reactivity and biological implications of the products of S-sulfhydration, i.e. persulfides, are still unclear. This is mainly due to the instability of persulfides and difficulty to access these molecules. Under physiological conditions persulfides mainly exist in anionic forms because of their low pKa values. However, current methods do not allow for the direct generation of persulfide anions under biomimetic and non-H2S conditions. Herein we report the development of a functional disulfide, FmSSPy-A (Fm =9-fluorenylmethyl; Py = pyridinyl). This reagent can effectively convert both small molecule and protein thiols (-SH) to form –S-SFm adducts under mild conditions. It allows for a H2S-free and biomimetic protocol to generate highly reactive persulfides (in their anionic forms). We also demonstrated the high nucleophilicity of persulfides toward a number of thiol-blocking reagents. This method holds promise for further understanding the chemical biology of persulfides and S-sulfhydration.

Research Organization:
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division
Grant/Contract Number:
AC05-76RL01830; R01HL116571; P41 GM103493
OSTI ID:
1239169
Alternate ID(s):
OSTI ID: 1337259
Report Number(s):
PNNL-SA-115055
Journal Information:
Organic Letters, Journal Name: Organic Letters Vol. 18 Journal Issue: 5; ISSN 1523-7060
Publisher:
American Chemical SocietyCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 52 works
Citation information provided by
Web of Science

References (25)

H2S Signals Through Protein S-Sulfhydration journal November 2009
Detection of Protein S-Sulfhydration by a Tag-Switch Technique journal November 2013
A Persulfide Analogue of the Nitrosothiol SNAP: Formation, Characterization and Reactivity journal September 2014
Hydrogen Sulfide Protects Against Cellular Senescence via S -Sulfhydration of Keap1 and Activation of Nrf2 journal May 2013
Redox chemistry and chemical biology of H2S, hydropersulfides, and derived species: Implications of their possible biological activity and utility journal December 2014
Physiological Implications of Hydrogen Sulfide: A Whiff Exploration That Blossomed journal April 2012
Biology and therapeutic potential of hydrogen sulfide and hydrogen sulfide-releasing chimeras journal March 2013
Understanding Hydrogen Sulfide Storage: Probing Conditions for Sulfide Release from Hydrodisulfides journal July 2014
Hydrogen sulfide-mediated cardioprotection: mechanisms and therapeutic potential journal December 2010
Amino Acid and Peptide Synthesis and Functionalization by the Reaction of Thioacids with 2,4-Dinitrobenzenesulfonamides journal October 2007
Hydrogen Sulfide Is a Signaling Molecule and a Cytoprotectant journal July 2012
A Practical Look at the Chemistry and Biology of Hydrogen Sulfide journal July 2012
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Hydrogen Sulfide and Cell Signaling journal February 2011
Hydrogen sulfide as a gasotransmitter journal April 2010
Evolutionary and comparative aspects of nitric oxide, carbon monoxide and hydrogen sulfide journal November 2012
Small Molecule Signaling Agents: The Integrated Chemistry and Biochemistry of Nitrogen Oxides, Oxides of Carbon, Dioxygen, Hydrogen Sulfide, and Their Derived Species journal February 2012
Persulfide Reactivity in the Detection of Protein S -Sulfhydration journal April 2013
Hydrogen Sulfide-Linked Sulfhydration of NF-κB Mediates Its Antiapoptotic Actions journal January 2012
Methylsulfonyl Benzothiazole (MSBT): A Selective Protein Thiol Blocking Reagent journal June 2012
Reactive cysteine persulfides and S-polythiolation regulate oxidative stress and redox signaling journal April 2014
Persulfides: current knowledge and challenges in chemistry and chemical biology journal January 2015
H2S-Induced Sulfhydration of the Phosphatase PTP1B and Its Role in the Endoplasmic Reticulum Stress Response journal December 2011
Hydrogen Sulfide in Biochemistry and Medicine journal July 2012
The reaction of H2S with oxidized thiols: Generation of persulfides and implications to H2S biology journal December 2011

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Related Subjects

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY
disulfides
reagents
thiols
peptides and proteins
chemical reactions