Interactions of platinum and ruthenium coordination complexes with pancreatic phospholipase A(2) and phospholipids investigated by MALDI TOF mass spectrometry.
Phospholipase A2 is involved in propagation of inflammatory processes and carcinogenesis through its role in phospholipid metabolism, and release of arachidonic acid and lysophospholipids. Recent findings on correlation between elevated PLA2 activity and metastatic cancer render this enzyme an attractive target for cancer therapy. On the other hand, due to a broad range of oxidation states under physiological conditions and a high affinity for protein binding, platinum and ruthenium coordination complexes are promising candidates for PLA2 inhibitors. In this article, we discuss the interactions of Pt and Ru coordination complexes with PLA2 and phospholipids, as well as the application of MALDI-TOF mass spectrometry for screening PLA2 inhibitors. Owing to the ability of this technique to simultaneously detect and monitor changes in substrate and product concentrations, the inhibitor mechanisms of both Pt and Ru complexes with various ligands were determined.
'Vinča' Institute of Nuclear Sciences, Department of Physical Chemistry, University of Belgrade, Mike Petrovića Alasa 12-14, RS-11001 Belgrade (phone: +381 11 3408 64; fax: +381 11 8066 434); Haukeland University Hospital, Laboratory of Clinical Biochemistry, Section of Clinical Pharmacology, Jonas Lies Vei 65, NO-5020 Bergen (phone: +47 46 572612; fax:+47 55 290 718). tina@vinca.rs.
Tina
T
Kamčeva
Maja
M
Radisavljević
Iva
I
Vukićević
Jürgen
J
Arnhold
Marijana
M
Petković
D000818:Animals; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D010179:Pancreas / Q000201:enzymology; D064801:Phospholipase A2 Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D054467:Phospholipases A2 / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D010984:Platinum / Q000737:chemistry / Q000494:pharmacology*; D012428:Ruthenium / Q000737:chemistry / Q000494:pharmacology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013552:Swine
D056831:Coordination Complexes; D064801:Phospholipase A2 Inhibitors; D010743:Phospholipids; D010984:Platinum; D012428:Ruthenium; D054467:Phospholipases A2
Inhibitors; Mass spectrometry; Phospholipase A; Phospholipids; Platinum complexes; Ruthenium complexes