TY - JOUR
T1 - Stability of an organometallic ruthenium-ubiquitin adduct in the presence of glutathione
T2 - Relevance to antitumour activity
AU - Hartinger, Christian G.
AU - Casini, Angela
AU - Duhot, Céline
AU - Tsybin, Yury O.
AU - Messori, Luigi
AU - Dyson, Paul J.
N1 - Funding Information:
The authors are indebted to the FWF – Austrian Science Fund (C.G.H. Schrödinger Fellowship J2613-N19), and COST D39 (short term scientific mission for A.C.). A.C. thanks the AIRC for providing her with a research fellowship.
PY - 2008/12
Y1 - 2008/12
N2 - The interactions of the ruthenium(II) complex Ru(η6-p-cymene)(pta)Cl2 (RAPTA-C), an effective anticancer and antimetastatic agent, with biological nucleophiles are important with respect to its mechanism of action, for example, the reaction with glutathione (GSH) potentially plays an important role in detoxification. RAPTA-C reacts rapidly with glutathione forming a series of adducts including Ru(η6-p-cymene)(pta)(GS), Ru(η6-p-cymene)(GS) and bis-GSH conjugates, which were characterised by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). In addition, the ability of glutathione to cleave ruthenium-ubiquitin bonds was assayed and it was shown that GSH is capable of removing the Ru moiety from the protein, although no ternary adducts were identified.
AB - The interactions of the ruthenium(II) complex Ru(η6-p-cymene)(pta)Cl2 (RAPTA-C), an effective anticancer and antimetastatic agent, with biological nucleophiles are important with respect to its mechanism of action, for example, the reaction with glutathione (GSH) potentially plays an important role in detoxification. RAPTA-C reacts rapidly with glutathione forming a series of adducts including Ru(η6-p-cymene)(pta)(GS), Ru(η6-p-cymene)(GS) and bis-GSH conjugates, which were characterised by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). In addition, the ability of glutathione to cleave ruthenium-ubiquitin bonds was assayed and it was shown that GSH is capable of removing the Ru moiety from the protein, although no ternary adducts were identified.
KW - Anticancer drugs
KW - Bioorganometallic chemistry
KW - FT-ICR mass spectrometry
KW - Glutathione
KW - Ruthenium complex
UR - http://www.scopus.com/inward/record.url?scp=55349148309&partnerID=8YFLogxK
U2 - 10.1016/j.jinorgbio.2008.08.002
DO - 10.1016/j.jinorgbio.2008.08.002
M3 - Article
C2 - 18834634
AN - SCOPUS:55349148309
SN - 0162-0134
VL - 102
SP - 2136
EP - 2141
JO - Journal of Inorganic Biochemistry
JF - Journal of Inorganic Biochemistry
IS - 12
ER -