The studentship will focus on the computational development of covalent inhibition strategies for sulfenic acid
, sulfenyl amide, and S-nitrosylated cysteines.
The reversible formation of sulfinic and sulfenic acid
maintains the redox state of the plasma to the moderate, unprolonged exposure to OS .
Inside the intact cells of an onion, a molecule called sulfenic acid
precursor floats around the watery filler like a napping human in a lazy river.
However, in a series of studies aimed at clarifying the antioxidant activity of garlic-derived thiosulfinates similar to allicin (1), it was discovered that the active molecule able to trap peroxyl radical was not (1) itself, but the sulfenic acid
that derives from its decomposition by Cope elimination (Scheme 5) [46, 47].
[H.sub.2][O.sub.2] thiol groups on cysteine residues to produce sulfenic acid
Typical 2-Cys Prxs (Prx1-Prx4) are active as dimers organized in antiparallel fashion: that is, the peroxidatic cysteine residue ([C.sub.P]) in the amino terminus of one subunit reacts with the hydroperoxides and the resulting Cp sulfenic acid
forms a disulfide linkage with the sulfhydryl group of resolving cysteine residue ([C.sub.R]) in carboxyl terminus of another subunit .
Redox-active cysteine residues in protein are subject to more than one kind of modification, which include disulfide, glutathionyl, nitrosyl, or sulfenic acid
modification [61, 62].
Garlic contains the compound allicin, which releases the powerful antioxidant sulfenic acid
as it is broken down by the body.
The new method detects sulfenic acid
in proteins-a tip off to early oxidative stress and to a specific protein modification associated with cell growth pathways.
During the decomposition of allicin, sulfenic acid
is formed, which acts as a free radical scavenger.
Monosulfidic crosslinks are expected to decompose into sulfenic acid
derivatives, which are postulated as powerful antioxidants (ref.
Susceptible cysteine residues in redoxsensitive proteins exist as a thiolate anion in a physiological pH and they can be reversibly oxidized by hydrogen peroxide to yield sulfenic acid