The antioxidant activity of the biochalcogens sulfur and selenium is important to reducing the risk for cancer, cardiovascular disease, and other chronic illnesses. The active sites of thio- and selenoproteins often contain a C(X)­­nC(U) (n = 0-2) motif, where C = Cys, U = SeCys, and the spacer residue X varies with protein function. It has recently been shown that different conformations of the selenenylsulfide ring formed through the oxidation of these motifs can be detected through 77Se NMR and identified through DFT calculations of the 77Se chemical shift of model compounds. In this study, molecular dynamics (MD) simulations in AMBER are used to propagate the conformations of the disulfides CGGC and CGAC to understand the affect that spacer residues have on the oxidized form of thio- and selenoproteins. Unique conformations of the disulfide and the selenenylsulfide analogues were optimized using density functional theory (DFT). GIAO-DFT calculations were used to calculate the 77Se chemical shifts for comparison to experimental data. The theoretical chemical shifts for different conformations were in excellent argreement with resonances observed in the experimental 77Se spectrum of CGAU-containing selenopeptides.

Conformational analysis of cyclic disulfides and selenenyl sulfides in peptide redox motifs

249th National Meeting (2015)

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