Interactions of alkyltin salts with biological dithiols: dealkylation and induction of a regular beta-turn structure in peptides.

Organotin compounds specifically target vicinal dithiols, thereby inhibiting the function of essential enzymes. Here, we present the NMR binding studies of trimethyltin (TMT) and dimethyltin (DMT) chlorides with a linear peptide (ILGCWCYLR) derived from the membrane protein stannin (SNN). We show that this peptide is able to dealkylate TMT and bind DMT, adopting a stable type-I beta-turn conformation. Both the NMR data and the calculated structures indicate that the two cysteines coordinate the tin atom in a distorted tetrahedral geometry. The molecular geometries and tin coordination state were confirmed using density functional theory (DFT). In addition, NMR spectral parameters back calculated from the DFT minimized structure compared well with experimental data. These results in conjunction with studies on peptide variants (i.e., C4S, C6S, and Y7F) demonstrate unequivocally the key role of biological dithiols in both the dealkylation and binding of organotin compounds. This peptide serves as a model system for alkyltin-protein interactions and gives new insights into the biological fate of alkyltin compounds.