Cisplatin interaction with amino acids cysteine and methionine from gas phase to solutions with constant pH

Zimmermann, Tomáš; Burda, Jaroslav V.

doi:10.1007/s12539-010-0094-x

Cited by 16 publications

(16 citation statements)

References 94 publications

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“…However, 90% of their reported binding is to plasma proteins (Fischer et al, 2008). A variety of different proteins have been studied for their binding affinity to cisplatin using either mass spectrometry or X-ray diffraction, including a copper transporter (Arnesano & Natile, 2008;Crider et al, 2010), a copper chaperone (Boal & Rosenzweig, 2009), superoxide dismutase (Calderone et al, 2006;Casini et al, 2008), cytochrome c (Casini et al, 2006;, human albumin (Ivanov et al, 1998), ubiquitin (Hartinger et al, 2007, glutathione reductase (Zimmermann & Burda, 2010), Na + /K + -ATPase (Huličiak et al, 2012) and hen egg-white lysozyme (HEWL; . Carboplatin binding affinity, however, has been less studied, with one study using mass spectrometry and another study involving X-ray diffraction , both of which looked at binding to HEWL.…”

Section: Introductionmentioning

confidence: 99%

Room-temperature X-ray diffraction studies of cisplatin and carboplatin binding to His15 of HEWL after prolonged chemical exposure

et al. 2012

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The anticancer complexes cisplatin and carboplatin are known to bind to both the Nδ and the Nℇ atoms of His15 of hen egg-white lysozyme (HEWL) in the presence of dimethyl sulfoxide (DMSO). However, neither binds in aqueous media after 4 d of crystallization and crystal growth, suggesting that DMSO facilitates cisplatin/carboplatin binding to the N atoms of His15 by an unknown mechanism. Crystals of HEWL cocrystallized with cisplatin in both aqueous and DMSO media, of HEWL cocrystallized with carboplatin in DMSO medium and of HEWL cocrystallized with cisplatin and N-acetylglucosamine (NAG) in DMSO medium were stored for between seven and 15 months. X-ray diffraction studies of these crystals were carried out on a Bruker APEX II home-source diffractometer at room temperature. Room-temperature X-ray diffraction data collection removed the need for cryoprotectants to be used, ruling out any effect that the cryoprotectants might have had on binding to the protein. Both cisplatin and carboplatin still bind to both the Nδ and Nℇ atoms of His15 in DMSO media as expected, but more detail for the cyclobutanedicarboxylate (CBDC) moiety of carboplatin was observed at the Nℇ binding site. However, two molecules of cisplatin were now observed to be bound to His15 in aqueous conditions. The platinum peak positions were identified using anomalous difference electron-density maps as a cross-check with Fo-Fc OMIT electron-density maps. The occupancies of each binding site were calculated using SHELXTL. These results show that over time cisplatin binds to both N atoms of His15 of HEWL in aqueous media, whereas this binding is speeded up in the presence of DMSO. The implication of cisplatin binding to proteins after a prolonged period of time is an important consideration for the length of treatment in patients who are given cisplatin.

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Section: Introductionmentioning

confidence: 99%

Room-temperature X-ray diffraction studies of cisplatin and carboplatin binding to His15 of HEWL after prolonged chemical exposure

et al. 2012

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“…Glutathione (L-g-glutamyl-l-cysteinyl-glycine, GSH) plays a vital role in the cellular redox state via scavenging free radicals, defending cells against xenobiotics and maintaining the sulfhydryl groups of many proteins (Brozovic et al, 2010). The active SH-group of GSH has a high affinity to platinum, thus makes GSH become an easy, non-DNA-related target (Zimmermann and Burda, 2010). The GSplatinum complex catalyzed by glutathione-S-transferase can reach to about 60% of the intracellular platinum content after 12-h incubation in leukemia cells (Ishikawa and Ali-Osman, 1993), and the elevated expression of GSH and glutathione-S-transferase are often seen in the resistant-cells (Masters et al, 1996;Byun et al, 2005).…”

Section: Detoxification System Glutathionementioning

confidence: 99%

The Drug-Resistance Mechanisms of Five Platinum-Based Antitumor Agents

et al. 2020

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Platinum-based anticancer drugs, including cisplatin, carboplatin, oxaliplatin, nedaplatin, and lobaplatin, are heavily applied in chemotherapy regimens. However, the intrinsic or acquired resistance severely limit the clinical application of platinum-based treatment. The underlying mechanisms are incredibly complicated. Multiple transporters participate in the active transport of platinum-based antitumor agents, and the altered expression level, localization, or activity may severely decrease the cellular platinum accumulation. Detoxification components, which are commonly increasing in resistant tumor cells, can efficiently bind to platinum agents and prevent the formation of platinum-DNA adducts, but the adducts production is the determinant step for the cytotoxicity of platinum-based antitumor agents. Even if adequate adducts have formed, tumor cells still manage to survive through increased DNA repair processes or elevated apoptosis threshold. In addition, autophagy has a profound influence on platinum resistance. This review summarizes the critical participators of platinum resistance mechanisms mentioned above and highlights the most potential therapeutic targets or predicted markers. With a deeper understanding of the underlying resistance mechanisms, new solutions would be produced to extend the clinical application of platinum-based antitumor agents largely.

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“…Only a handful of other proteins have been studied for their affinity to bind cisplatin, including copper transporter (Arnesano & Natile, 2008;Crider et al, 2010), superoxide dismutase (Calderone et al, 2006;Casini et al, 2008), cytochrome c (Casini et al, 2006;, human albumin (Ivanov et al, 1998), ubiquitin (Hartinger et al, 2006), human copper chaperone (Boal & Rosenzweig, 2009) and glutathione (Zimmermann & Burda, 2010). These studies mostly used MS to confirm the binding of cisplatin to specific Met/Cys or His residues, with only the X-ray crystal structures of cisplatin bound to HEWL , to a copper chaperone (Boal & Rosenzweig, 2009) and to superoxide dismutase being available (Calderone et al, 2006;Casini et al, 2008).…”

Section: Comparison With Other Proteins Binding Cisplatin and Implicamentioning

confidence: 99%

“…Binding affinity to cisplatin has been studied for a number of proteins, including a copper transporter (Arnesano & Natile, 2008;Crider et al, 2010), a copper chaperone (Boal & Rosenzweig, 2009), superoxide dismutase (Calderone et al, 2006;Casini et al, 2008), cytochrome c (Casini et al, 2006;, human albumin (Ivanov et al, 1998), ubiquitin (Hartinger et al, 2006), glutathione (Zimmermann & Burda, 2010) and hen egg-white lysozyme (HEWL; . The platinum ion is a soft ligand and makes favourable interactions with S atoms present in proteins through free methionine and cysteine side chains, forming strong bonds (Zimmermann & Burda, 2010;Hahn et al, 2001). However, HEWL and superoxide dismutase have free histidine (His) residues which can coordinate the Pt ion through an N atom on the imidazole ring (Calderone et al, 2006;Casini et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Structural studies of the effect that dimethyl sulfoxide (DMSO) has on cisplatin and carboplatin binding to histidine in a protein

Tanley

Schreurs

Kroon-Batenburg

et al. 2012

Acta Crystallogr D Biol Cryst

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The anticancer complexes cisplatin and carboplatin target the DNA major groove, forming intrastrand and interstrand cross-links between guanine bases through their N7 atoms, causing distortion of the DNA helix and apoptotic cell death. A major side effect of these drugs is toxicity, which is caused via binding to many proteins in the body. A range of crystallographic studies have been carried out involving the cocrystallization of hen egg-white lysozyme (HEWL) as a test protein with cisplatin and carboplatin in aqueous and dimethyl sulfoxide (DMSO) conditions. Different cryoprotectants, glycerol and Paratone, were used for each of the cisplatin and carboplatin cocrystallization cases, while silicone oil was used for studies involving N-acetylglucosamine (NAG). Both cisplatin and carboplatin do not bind to HEWL in aqueous media on the timescales of the conditions used here, but upon addition of DMSO two molecules of cisplatin or carboplatin bind either side of His15, which is the only His residue in lysozyme and is assumed to be an imidazolyl anion or a chemical resonance moiety, i.e. both imidazole N atoms are chemically reactive. To identify the platinum-peak positions in the 'with DMSO conditions', anomalous scattering maps were calculated as a cross-check with the F(o) - F(c) OMIT maps. Platinum-occupancy σ values were established using three different software programs in each case. The use of EVAL15 to process all of the diffraction data sets provided a consistent platform for a large ensemble of data sets for the various protein and platinum-compound model refinements with REFMAC5 and then SHELXTL. Overall, this extensive set of crystallization and cryoprotectant conditions allowed a systematic evaluation of cisplatin and carboplatin binding to lysozyme as a test protein via detailed X-ray crystal structure characterizations. DMSO is used as a super-solvent for drug delivery as it is deemed to cause no effect upon drug binding. However, these results show that addition of DMSO causes the platinum anticancer drugs to bind to HEWL. This effect should be considered in toxicity assessments of these drugs and perhaps more widely.

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Cisplatin interaction with amino acids cysteine and methionine from gas phase to solutions with constant pH

Cited by 16 publications

References 94 publications

Room-temperature X-ray diffraction studies of cisplatin and carboplatin binding to His15 of HEWL after prolonged chemical exposure

Room-temperature X-ray diffraction studies of cisplatin and carboplatin binding to His15 of HEWL after prolonged chemical exposure

The Drug-Resistance Mechanisms of Five Platinum-Based Antitumor Agents

Structural studies of the effect that dimethyl sulfoxide (DMSO) has on cisplatin and carboplatin binding to histidine in a protein

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