The reactions of cis-[Pt(NH3)2(H2O)2]2+ with L-(+)-cystathionine and seleno-L-methionine: potential relevance to the molecular basis of cisplatin toxicity.
NMR spectroscopic studies indicate that the hydrolysis product of cisplatin, cis-[Pt(NH3)2-(H2O)2]2+, reacts readily with the important intracellular thiol L-(+)-cystathionine and the amino acid derivative seleno-L-methionine. In both cases, the formation of six-membered mononuclear S,N- or Se, N-chelate rings was established on the basis of [1H], [13C], [77Se], [195Pt], and [13C]-(1H) DEPT (distortionless enhancement by polarization transfer), COSY (correlation spectroscopy), heterocorrelation, and NOE (nuclear Overhauser effect) difference NMR experiments. The formation of these products suggests that related in vivo processes may play a significant role in the toxicity of cisplatin. The potential loss of NH3 in such platinum complexes may lead to additional products over time.
Beaty
J A
JA
Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235.
Jones
M M
MM
Ma
L
L
D002945:Cisplatin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity*; D003540:Cystathionine / Q000737:chemistry*; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D012645:Selenomethionine / Q000737:chemistry*; D013237:Stereoisomerism
C034297:diamminediaqua platinum(II); D003540:Cystathionine; D012645:Selenomethionine; D002945:Cisplatin