Abstract
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.
Abbreviations
| PGP I | = |
Bacillus amyloliquefaciens pyroglutamyl-peptidase I |
| BP-Pt(II) | = |
Bipyridine platinum(II) |
| Cisplatin | = |
Cis-diamminedichloroplatinum(II) |
| Carboplatin | = |
Cis-diammine-1,1-cyclobutanedicarboxylate platinum(II) |
| CVB3 3Cpro | = |
Coxsackievrius stain B3 3Cpro |
| DHB | = |
2,5-Dihydroxybenzoic acid |
| DTT | = |
Dithiothreitol |
| GspA | = |
N-teminal amidase of glutathionyl-spermidine synthetase/amidase |
| GspSA | = |
Glutathionyl-spermidine synthetase/amidase |
| hTrxR | = |
Human thioredoxin reductase |
| IPTG | = |
Isopropyl β-D-1-thiogalactopyranoside |
| IC50 | = |
Inhibitory concentration at 50% inhibition |
| MALDI | = |
Matrix-assisted laser desorption/ionization |
| PDB | = |
Protein Data Bank |
| PGL | = |
Pyrogultaminal |
| RMSD | = |
Root mean square deviation |
| SeC | = |
Selenocysteine |
| TCEP | = |
Tris(2-carboxyethyl)phosphine |
| TGR | = |
Thioredoxin/glutathione reductase |
| TP-Pt(II) | = |
(2,2′:6′,2″-terpyridine)platinum(II) |
| TryR | = |
Try-panothione reductase |
| HTP-TP-Pt(II) | = |
(4-Hydroxylthiophenolato) (2,2′:6′,2″-terpyridine)platinum(II) |
| NAP-TP-Pt(II) | = |
(N-Acetyl-4-aminothiophenolato) (2,2′:6′,2″-terpyridine)platinum(II). |
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