title: Inhibitory effect of platinum and ruthenium bipyridyl complexes on porcine pancreatic phospholipase A2.
abstract: Pancreatic phospholipase A(2) (PLA(2)) plays an important role in cellular homeostasis as well as in the process of carcinogenesis. Effects of metallo-drugs used as chemotherapeutics on the activity of this enzyme are unknown. In this work, the interaction between porcine pancreatic PLA(2) and two selected transition metal complexes--tetrachloro(bipyridine) platinum(IV) ([PtCl(4)(bipy)]) and dichloro (bipyridine) ruthenium(III)chloride ([RuCl(2)(bipy)(2)]Cl)--was studied. Matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) and fluorescence spectroscopy have been used to analyse the enzyme activity in the absence and presence of metal complexes and to verify potential binding of these drugs to the enzyme. The tested metal complexes decreased the activity of phospholipase A(2) in an uncompetitive inhibition mode. A binding of the ruthenium complex near the active site of the enzyme could be evidenced and possible modes of interaction are discussed.
authors: Laboratory of Physical Chemistry, Institute of Nuclear Sciences Vinča, University of Belgrade, Mike Petrovića Alasa 12-14, Belgrade, Serbia. tina@vinca.rs
authors: Tina
authors: T
authors: Kamčeva
authors: Jörg
authors: J
authors: Flemmig
authors: Bojana
authors: B
authors: Damnjanović
authors: Jürgen
authors: J
authors: Arnhold
authors: Aleksandar
authors: A
authors: Mijatović
authors: Marijana
authors: M
authors: Petković
mesh_terms: D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000494:pharmacology*; D010179:Pancreas / Q000201:enzymology*; D064801:Phospholipase A2 Inhibitors; D054467:Phospholipases A2 / Q000378:metabolism*; D011485:Protein Binding; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013552:Swine
chemical_list: D004791:Enzyme Inhibitors; D009942:Organometallic Compounds; D009944:Organoplatinum Compounds; D064801:Phospholipase A2 Inhibitors; C103599:bis(bipyridyl)ruthenium(II); D015082:2,2'-Dipyridyl; D054467:Phospholipases A2