bi7b00751_si_001.pdf (4.25 MB)
Selenoglutathione Diselenide: Unique Redox Reactions in the GPx-Like Catalytic Cycle and Repairing of Disulfide Bonds in Scrambled Protein
journal contribution
posted on 2017-10-12, 13:56 authored by Shingo Shimodaira, Yuki Asano, Kenta Arai, Michio IwaokaSelenoglutathione
(GSeH) is a selenium analogue of naturally abundant
glutathione (GSH). In this study, this water-soluble small tripeptide
was synthesized in a high yield (up to 98%) as an oxidized diselenide
form, i.e., GSeSeG (1), by liquid-phase peptide synthesis
(LPPS). Obtained 1 was applied to the investigation of
the glutathione peroxidase (GPx)-like catalytic cycle. The important
intermediates, i.e., GSe– and GSeSG, besides GSeO2H were characterized by 77Se NMR spectroscopy.
Thiol exchange of GSeSG with various thiols, such as cysteine and
dithiothreitol, was found to promote the conversion to GSe– significantly. In addition, disproportionation of GSeSR to 1 and RSSR, which would be initiated by heterolytic cleavage
of the Se–S bond and catalyzed by the generated selenolate,
was observed. On the basis of these redox behaviors, it was proposed
that the heterolytic cleavage of the Se–S bond can be facilitated
by the interaction between the Se atom and an amino or aromatic group,
which is present at the GPx active site. On the other hand, when a
catalytic amount of 1 was reacted with scrambled 4S species
of RNase A in the presence of NADPH and glutathione reductase, native
protein was efficiently regenerated, suggesting a potential use of 1 to repair misfolded proteins through reduction of the non-native
SS bonds.