Organic Letters
Letter
Signaling 2009, 2, ra72. (b) Sen, N.; Paul, B. D.; Gadalla, M. M.;
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We then tested if this method could be used to form
persulfide adducts on specific cysteines in proteins. It is known
that nonreduced BSA has one free −SH (Cys34). Therefore,
nonreduced BSA was treated with 2 and followed by DBU/
IAM. The resultant protein intermediate and final product were
subjected to tryptic digestion and LC-MS/MS. Control samples
(without the treatment of 2) were also obtained and compared.
As shown in Figure 1, the formation of BSA-S-SFm on Cys34
was clearly identified by MS analysis (Figure 1B). Moreover, an
IAM-modified fragment on Cys34 was also observed (Figure
1C).
In summary, here we reported a novel functional disulfide
(i.e., compound 2) which could effectively convert small
molecule and protein thiols (−SH) to form −S-SFm adducts
under mild conditions. This allows for a H2S-free protocol (by
using DBU) to generate highly reactive persulfides in their
anionic forms. We also demonstrated the high nucleophilicity
of persulfides toward a number of thiol-blocking reagents. The
use of DBU in this process may, under some circumstances,
impact the reactivity studies. Nevertheless, this biomimetic
persulfide formation strategy should be useful in further
understanding the chemical biology of persulfides.
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ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
Experimental procedures, characterization data of all
compounds, MS/MS data for peptides 14, 16, and 19
AUTHOR INFORMATION
Corresponding Author
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the NIH (R01HL116571 and P41
GM103493). Part of the mass spectromtery analyses was
performed in the Environmental Molecular Sciences Labo-
ratory, a DOE national scientific user facility located at Pacific
Northwest National Laboratory, which is operated by Battelle
Memorial Institute for the DOE under Contract DE-AC05-
76RL01830.
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