Mass spectrometric studies of the formation and reactivity of trans-[PtCl₂(Am)(piperidinopiperidine)]·HCl complexes with ubiquitin

trans-[PtCl₂(Am)(pip-pip)]·HCl complexes, where Am = ammine, methylamine and dimethylamine, react with ubiquitin to form 1:1 covalent adducts. The platinum complexes bind exclusively to Met1 of ubiquitin forming trans-[PtCl(S-Met1-Ub)(Am)(pip-pip)] adducts. These adducts are reactive towards nucleophiles and react with deoxyguanosine (dGMP) to form the ternary trans-[Pt(dGMP)(S-Met1-Ub) (Am)(pip-pip)] complex which is stable in water and even in the presence of excess glutathione (GSH). Reaction of trans-[PtCl(S-Met1-Ub)(Am)(pip-pip)] with GSH resulted in the rapid formation of the ternary complex trans-[Pt(GS)(S-Met1-Ub)(Am)(pip-pip)] which was not stable and slowly lost the platinum moiety; after 7 days the platinum moiety was completely removed and the native ubiquitin was regenerated.