Ligand effects on the binding of cis- and trans-[PtCl2Am1Am2 to proteins

Yousef Najajreh, Tal Peleg-Shulman, Ofra Moshel, Nicholas Farrel, Dan Gibson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

As part of a systematic study of the basic principles that govern the formation and reactivity of Pt-protein adducts, we report the effect of substituting the ammine ligand of cis- and trans-[PtCl2(NH3)2] complexes with bulkier planar aromatic or nonplanar cyclic amine ligands on the binding properties of the complexes to ubiquitin and to horse heart myoglobin. The ligand replacement had a different effect on the cis or trans isomers investigated. In the cis-Pt complexes, replacing one or both ammine ligands by piperidine or 4-picoline dramatically decreased the binding of the complexes to the proteins studied, whereas in the substituted trans-Pt complexes replacement of the ammine by a piperidine or 4-picoline increased the binding rate. This behavior may have to do with the different preferred binding sites of the cis- and trans-Pt complexes. The bulkier cis- or trans-Pt complexes investigated also did not display a preference for Met1 of ubiquitin, possibly owing to steric constraints imposed by the substituted ligands. The introduction of a charged piperazine ligand significantly decreased the rate of binding to the protein, possibly owing to electrostatic interactions or hydrogen-bond formations with the surface of the protein. The binding of the complexes to ubiquitin and myoglobin does not disrupt the folding of the proteins as judged by electrospray ionization mass spectrometry.

Original languageEnglish
Pages (from-to)167-175
Number of pages9
JournalJournal of Biological Inorganic Chemistry
Volume8
Issue number1-2
DOIs
StatePublished - Jan 2003

Keywords

  • Electrospray ionization mass spectrometry
  • Kinetics
  • Ligand effects
  • Platinum complexes
  • Protein binding

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