Mass spectrometric studies of the formation and reactivity of trans-[PtCl2(Am)(piperidinopiperidine)] x HCl complexes with ubiquitin.
trans-[PtCl2(Am)(pip-pip)] x 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.
Balter
Liliana
L
Department of Medicinal Chemistry and Natural Products, School of Pharmacy, P.O. Box 12065, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
Gibson
Dan
D
D001665:Binding Sites; D013058:Mass Spectrometry; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D013997:Time Factors; D025801:Ubiquitin / Q000737:chemistry* / Q000378:metabolism
D009944:Organoplatinum Compounds; D025801:Ubiquitin