Terpyridine platinum(ii) complexes inhibit cysteine proteases by binding to active-site cysteine

Yan Chung Lo, Wen Chi Su, Tzu Ping Ko, Nai Chen Wang, Andrew H.J. Wang

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


Platinum(II) complexes have been demonstrated to form covalent bonds with sulfur-donating ligands (in glutathione, metallothionein and other sulfur-containing biomolecules) or coordination bonds with nitrogen-donating ligands (such as histidine and guanine). To investigate how these compounds interact with cysteine proteases, we chose terpyridine platinum(II) (TP-Pt(II)) complexes as a model system. By using X-ray crystallography, we demonstrated that TP-Pt(II) formed a covalent bond with the catalytic cysteine residue in pyroglutamyl peptidase I. Moreover, by using MALDI (matrix-assisted laser desorption/ionization) and TOF-TOF (time of flight) mass spectrometry, we elucidated that the TP-Pt(II) complex formed a covalent bond with the active-site cysteine residue in two other types of cysteine protease. Taken together, the results unequivocally showed that TP-Pt(II) complexes can selectively bind to the active site of most cysteine proteases. Our findings here can be useful in the design of new anti-cancer, anti-parasite or anti-virus platinum(II) compounds.

Original languageEnglish
Pages (from-to)267-282
Number of pages16
JournalJournal of Biomolecular Structure and Dynamics
Issue number2
Publication statusPublished - Oct 2011
Externally publishedYes


  • Crystal structure
  • Cysteine protease inhibitors
  • Enzyme activity
  • Platinum(II)

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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