Comparative reactivity of medicinal gold(i) compounds with the cyclic peptide vasopressin and its diselenide analogue

The reactions of the medicinal gold(i) compound auranofin and its close analogues with vasopressin and the diselenide analogue were comparatively investigated by LC-electrospray MS/MS. Evidence is gained of the possible cleavage of the S-S and Se-Se bridges induced by Au(i). Notably, we found that, in the absence of reducing agents, the sulfur and selenium atoms are metallated only at high temperature (70 degrees C) with the preferential binding of gold to selenium. The reaction with the S-S bridge can take place at physiological temperature (37 degrees C) under reducing conditions. The implications of these results are discussed in the general frame of the reactivity of biologically relevant soft Lewis acids with peptides and proteins.

Automated summary

The reactions of medicinal gold(i) compound auranofin and its analogues with vasopressin and the diselenide analogue were investigated using LC-electrospray MS/MS. Evidence suggested that Au(i) could induce the cleavage of S-S and Se-Se bridges. Notably, metallation of sulfur and selenium atoms only occurred at high temperatures, with preferential binding of gold to selenium. The implications of these findings were discussed in terms of the reactivity of soft Lewis acids with peptides and proteins.