JBIC Journal of Biological Inorganic Chemistry (v.15, #7)
Structural basis for the decrease in the outward potassium channel current induced by lanthanum by Li Hong Wang; Na Jiang; Bo Zhao; Xiao Dong Li; Tian Hong Lu; Xiao Lan Ding; Xiao Hua Huang (989-993).
The current of the outward K+ channel in the cell of horseradish treated with La3+ and the direct interaction between La3+ and the K+ channel protein were investigated using the whole-cell patch-clamp technique, molecular dynamics simulation, and quantum chemistry calculation methods. It was found for the first time that La3+ decreases the current of the K+ channel in the horseradish mesophyll cell. The decrease results from the formation of a coordination bond and hydrogen bond between La3+ and the K+ channel protein in the plasma membrane. The direct interaction destroys the native structure of the K+ channel protein, disturbing the function of the K+ channel protein in the cells. The results can provide the theoretical foundation for understanding the interaction between metal ions (especially high-valence metal ions) and the channel protein in organisms, including animal and plant cells.
Keywords: High-valence metal; Channel protein; Patch clamp; Molecular dynamics simulation; Quantum chemistry calculation
Critical role of tyrosine 79 in the fluorescence resonance energy transfer and terbium(III)-dependent self-assembly of ciliate Euplotes octocarinatus centrin by Lian Duan; Wen Liu; Zhi-Jun Wang; Ai-Hua Liang; Bin-Sheng Yang (995-1007).
Ciliate Euplotes octocarinatus centrin (EoCen) is a member of the EF-hand superfamily of calcium-binding proteins. It has been proven, using Tb3+ as a fluorescence probe, that EoCen has four calcium-binding sites. The sensitized emission arises from nonradiative energy transfer between the three tyrosine residues (Tyr46, Tyr72, and Tyr79) of the N-terminal half and the bound Tb3+ ions. To determine the most critical of the three tyrosine residues for the process of fluorescence resonance energy transfer, six mutants of the N-terminal domain of EoCen, which contain one (N-Tyr46/N-Tyr72/N-Tyr79) or two (N-Y46F/N-Y72F/N-Y79F) tyrosine residues, were obtained by site-directed mutagenesis. The aromatic residue-sensitized Tb3+ fluorescence of N-Y79F was most affected, displaying a 50% reduction compared with wild-type N-EoCen. Among the tyrosines, Tyr79 is the shortest mean distance from the protein-bound Tb3+ (at sites I/II), as calculated via the Förster mechanism. The steady-state and time-resolved fluorescence parameters of the wild-type N-EoCen and the three double mutants suggest that Tyr79, which exists in a hydrophobic environment, has the highest quantum yield and a relatively long average lifetime. The decay of Tyr79 is the least heterogeneous among the three tyrosine residues. In addition, molecular modeling shows that a critical hydrogen bond is formed between the 4-hydroxyl group of Tyr79 and the oxygen from the side chains of the residue Asn39. Kinetic experiments on tyrosine and Tb3+ fluorescence demonstrate that tyrosine fluorescence quenching is largely due to the self-assembly of EoCen, and that the quenching degrees of the mutants differ. Resonance light scattering and crosslinking analysis carried out on the full-length single mutants (Y46F, Y72F, and Y79F) showed that Tyr79 also plays the most important role in the Tb3+-dependent self-assembly of EoCen among the three tyrosines.
Keywords: Centrin; Tyrosine; Terbium(III); Fluorescence resonance energy transfer; Self-assembly
Solution behavior of hematin under acidic conditions and implications for its interactions with chloroquine by Maria P. Crespo; Leann Tilley; Nectarios Klonis (1009-1022).
During the intraerythrocytic stage of its lifecycle, the malaria parasite digests host erythrocyte hemoglobin, producing free ferriprotoporhyrin IX (FP). Crystallization of FP into hemozoin is essential for its detoxification and is the target of quinoline antimalarials. To gain further insight into the mechanism of hemozoin formation and quinoline action we have studied the behavior of FP and related derivatives in 40% methanol in water at different concentrations across a broad pH range (2–12). The complex behavior of FP can be modeled by incorporating a pH-dependent dimerization constant that reflects the influence of the ionization state of the propionate groups on the level of self-association. The analysis reveals that aqua-ligated FP has a low propensity to self-associate and that the predominant self-associated species are homodimeric hydroxide-ligated FP and heterodimeric aqua/hydroxide-ligated FP. The latter is predicted to be the main self-associated species at the pH of the parasite digestive vacuole. The state of FP also affects its interaction with chloroquine, with maximum affinity under neutral conditions and a more than 1,000-fold decrease in affinity under acidic (pH 2) and basic (pH 12) conditions. First-derivative absorption spectra of the chloroquine–FP complex indicate that the high-affinity interaction requires the chloroquine ring in its neutral aminoquinoline form and this in turn requires at least one of the FP species in the complex to be aqua-ligated.
Keywords: Malaria; Ferriporphyrin; Hemozoin; Chloroquine; Absorption spectroscopy
Soluble artificial metalloproteases with broad substrate selectivity, high reactivity, and high thermal and chemical stabilities by Min Gyum Kim; Sang Ho Yoo; Woo Suk Chei; Tae Yeon Lee; Hye Mi Kim; Junghun Suh (1023-1031).
To design soluble artificial proteases that cleave peptide backbones of a wide range of proteins with high reactivity, artificial active sites comprising the Cu(II) complex of 1-oxa-4,7,10-triazacyclodedecane (oxacyclen) and the aldehyde group were synthesized. The aldehyde group was employed as the binding site in view of its ability to reversibly form imine bonds with ammonium groups exposed on the surfaces of proteins, and Cu(II) oxacyclen was exploited as the catalytic group for peptide hydrolysis. The artificial metalloproteases synthesized in the present study cleaved all of the protein substrates examined (albumin, γ-globulin, myoglobin, and lysozyme). In addition, the activity of the best soluble artificial protease was enhanced by up to 190-fold in terms of k cat/K m. When the temperature was raised to 80 °C, the activities of the artificial proteases were significantly enhanced. The activity of the artificial protease was not greatly affected by surfactants, including sodium dodecyl sulfate. The intermediacy of the imine complex formed between the artificial protease and the protein substrate was supported by an experiment using sodium cyanoborohydride. Soluble artificial metalloproteases with broad substrate selectivity, high reactivity, high thermal and chemical stabilities, and small molecular weights were thus synthesized by positioning the aldehyde group in proximity to Cu(II) oxacyclen.
Keywords: Proteolysis; Cu(II) oxacyclen; Artificial metalloprotease; Peptide-cleaving catalyst; Proteins
Methionine motifs of copper transport proteins provide general and flexible thioether-only binding sites for Cu(I) and Ag(I) by Jeffrey T. Rubino; Pamela Riggs-Gelasco; Katherine J. Franz (1033-1049).
Cellular acquisition of copper in eukaryotic organisms is primarily accomplished through high-affinity copper transport proteins (Ctr). The extracellular N-terminal regions of both human and yeast Ctr1 contain multiple methionine residues organized in copper-binding Mets motifs. These motifs comprise combinations of methionine residues arranged in clusters of MXM and MXXM, where X can be one of several amino acids. Model peptides corresponding to 15 different Mets motifs were synthesized and determined to selectively bind Cu(I) and Ag(I), with no discernible affinity for divalent metal ions. These are rare examples of biological thioether-only metal binding sites. Effective dissociation constant (K D) values for the model Mets peptides and Cu(I) were determined by an ascorbic acid oxidation assay and validated through electrospray ionization mass spectrometry and range between 2 and 11 μM. Affinity appears to be independent of pH, the arrangement of the motif, and the composition of intervening amino acids, all of which reveal the generality and flexibility of the MX1–2MX1–2M domain. Circular dichroism spectroscopy, 1H-NMR spectroscopy, and X-ray absorption spectroscopy were also used to characterize the binding event. These results are intended to aid the development of the still unknown mechanism of copper transport across the cell membrane.
Keywords: Copper; Silver; Methionine; Copper transport; Ctr
The effect of phosphate accumulation on metal ion homeostasis in Saccharomyces cerevisiae by Leah Rosenfeld; Amit R. Reddi; Edison Leung; Kimberly Aranda; Laran T. Jensen; Valeria C. Culotta (1051-1062).
Much of what is currently understood about the cell biology of metals involves their interactions with proteins. By comparison, little is known about interactions of metals with intracellular inorganic compounds such as phosphate. Here we examined the role of phosphate in metal metabolism in vivo by genetically perturbing the phosphate content of Saccharomyces cerevisiae cells. Yeast pho80 mutants cannot sense phosphate and have lost control of phosphate uptake, storage, and metabolism. We report here that pho80 mutants specifically elevate cytosolic and nonvacuolar levels of phosphate and this in turn causes a wide range of metal homeostasis defects. Intracellular levels of the hard-metal cations sodium and calcium increase dramatically, and cells become susceptible to toxicity from the transition metals manganese, cobalt, zinc, and copper. Disruptions in phosphate control also elicit an iron starvation response, as pho80 mutants were seen to upregulate iron transport genes. The iron-responsive transcription factor Aft1p appears activated in cells with high phosphate content in spite of normal intracellular iron levels. The high phosphate content of pho80 mutants can be lowered by mutating Pho4p, the transcription factor for phosphate uptake and storage genes. Such lowering of phosphate content by pho4 mutations reversed the high calcium and sodium content of pho80 mutants and prevented the iron starvation response. However, pho4 mutations only partially reversed toxicity from heavy metals, representing a novel outcome of phosphate dysregulation. Overall, these studies underscore the importance of maintaining a charge balance in the cell; a disruption in phosphate metabolism can dramatically impact on metal homeostasis.
Keywords: Yeast; Manganese; Aft1; Pho80; Polyphosphate
Molecular and cellular mechanism of the effect of La(III) on horseradish peroxidase by Lihong Wang; Qing Zhou; Tianhong Lu; Xiaolan Ding; Xiaohua Huang (1063-1069).
Horseradish is an important economic crop. It contains horseradish peroxidase (HRP) and lots of nutrients, and has specific pungency. Lanthanum is one of the heavy metals in the environment. It can transfer through the food chain to humans. In this paper, the molecular and cellular mechanism of the toxic effects of La(III) on HRP in vivo was investigated with an optimized combination of biophysical, biochemical, and cytobiological methods. It was found that La(III) could interact with O and/or N atoms in the backbone/side chains of the HRP molecule in the cell membrane of horseradish treated with 80 μM La(III), leading to the formation of a new complex of La and HRP (La–HRP). The formation of the La–HRP complex causes the redistribution of the electron densities of atoms in the HRP molecule, especially the decrease in the electron density of the active center, Fe(III), in the heme group of the La–HRP molecule compared with the native HRP molecule in vivo. Therefore, the electron transfer and the activity of HRP in horseradish treated with 80 μM La(III) are obviously decreased compared with those of the native HRP in vivo. This is a possible molecular and cellular mechanism for the toxic effect of La(III) on HRP in vivo. It is suggested that the accumulation of La in the environment, especially the formation of the La–HRP complex in vivo, is harmful to organisms.
Keywords: Heavy metal; Rare earth elements; Toxic effect; Biomarker; Horseradish peroxidase
The annotation of full zinc proteomes by Ivano Bertini; Leonardo Decaria; Antonio Rosato (1071-1078).
We obtained an extended functional annotation of zinc proteins using a combination of bioinformatic methods. This work was performed using a number of available predicted zinc proteomes of various representative organisms, leading to the almost complete annotation of, among others, the predicted human zinc proteome. The computational tools exploited included sequence-based and, when possible, structure-based functional predictions. We assigned a hypothetical function to 74% of the 1,472 sequences analyzed that lacked annotation in the starting dataset. We also added new functional categories, not described in the reference dataset, such as ubiquitin binding and DNA replication. As a general conclusion, we can state that the quality of each functional prediction parallels the amount of information for the sequence analyzed: the larger the amount of information, the more detailed and reliable is the proposed functional prediction. Among the findings, we have propose a zinc binding site for archaeal zinc-importing proteins. Furthermore, we propose two groups of transcriptional regulators that are involved in fatty acid metabolism.
Keywords: Zinc; Metalloproteomics; Metalloproteome; Zinc finger
Molecular interaction between europium decatungstate and histone H1 and its application as a novel biological labeling agent by Li Zheng; Zhanjun Gu; Ying Ma; Guangjin Zhang; Jiannian Yao; Bineta Keita; Louis Nadjo (1079-1085).
Polyoxometalates (POMs) show promising biological activities, but the mechanism of potential therapeutic effects remains to be elucidated at a molecular level. As a step toward the elucidation of the mechanistic pathways governing the bioactivity of POMs, the interaction between Eu-containing decatungstate [EuW10O36]9− (EuW10) and histone H1 has been studied. Fluorescence/luminescence analysis showed the existence of a strong interaction between EuW10 and histone H1. This interaction has key effects both on the luminescence of EuW10 and on the structure of histone H1. A gradual and intense enhancement of EuW10 luminescence was observed upon addition of increasing concentrations of histone H1. Circular dichroism investigations indicated that the binding of EuW10 significantly alters the secondary structure of histone H1. The present work is meaningful in finding novel labeling agents for fluorescence/luminescence or solid-state bioimaging.
Keywords: Lanthanide polyoxometalates; Histone H1; Luminescence; Fluorescence; Molecular interaction; Biolabel
Vanadium compounds discriminate hepatoma and normal hepatic cells by differential regulation of reactive oxygen species by Qin Wang; Tong-Tong Liu; Ying Fu; Kui Wang; Xiao-Gai Yang (1087-1097).
Our previous study indicated that vanadium compounds can block cell cycle progression at the G1/S phase in human hepatoma HepG2 cells via a highly activated extracellular signal-regulated protein kinase (ERK) signal. To explore their differential action on normal cells, we investigated the response of an immortalized hepatic cell line, L02 cells. The results demonstrated that a higher concentration of vanadium compounds was needed to inhibit L02 proliferation, which was associated with S and G2/M cell cycle arrest. In addition, in contrast to insignificant reactive oxygen species (ROS) generation in HepG2 cells, all of the vanadium compounds resulted significant increases in both O 2 ·− and H2O2 levels in L02 cells. At the same time, ERK and c-Jun N-terminal kinase (JNK) as well as cell division control protein 2 homolog (Cdc2) were found to be highly phosphorylated, which could be counteracted with the antioxidant N-acetylcysteine (NAC). The current study also demonstrated that both the ERK and the JNK pathways contributed to the cell cycle arrest induced by vanadium compounds in L02 cells. More importantly, it was found that although NAC can ameliorate the cytotoxicity of vanadium compounds in L02 cells, it did not decrease their cytotoxicity in HepG2 cells. It thus shed light on the potential therapeutic applications of vanadium compounds with antioxidants as synergistic agents to reduce their toxicities in human normal cells without affecting their antitumor activities in cancer cells.
Keywords: Vanadium compounds; Reactive oxygen species; Antioxidant; Cell cycle arrest
First structural evidence for the mode of diffusion of aromatic ligands and ligand-induced closure of the hydrophobic channel in heme peroxidases by Amit K. Singh; Nagendra Singh; Ashutosh Tiwari; Mau Sinha; Gajraj S. Kushwaha; Punit Kaur; A. Srinivasan; Sujata Sharma; T. P. Singh (1099-1107).
The mode of binding of aromatic ligands in the substrate binding site on the distal heme side in heme peroxidases is well understood. However, the mode of diffusion through the extended hydrophobic channel and the regulatory role of the channel are not yet clear. To provide answers to these questions, the crystal structure of the complex of lactoperoxidase and 3-amino-1,2,4-triazole (amitrole) has been determined, which revealed the presence of two ligand molecules, one in the substrate binding site and the second in the hydrophobic channel. The binding of ligand in the channel induced a remarkable conformational change in the side chain of Phe254, which flips from its original distant position to interact with the trapped ligand in the hydrophobic channel. As a result, the channel is completely blocked so that no ligand can diffuse through it to the substrate binding site. Another amitrole molecule is bound to lactoperoxidase in the substrate binding site by replacing three water molecules, including the crucial iron-bound water molecule, W1. In this arrangement, the amino nitrogen atom of amitrole occupies the position of W1 and interacts directly with ferric iron. As a consequence, it prevents the binding of H2O2 to heme iron. Thus, the interactions of amitrole with lactoperoxidase obstruct both the passage of ligands through the hydrophobic channel as well as the binding of H2O2. This explains the amitrole toxicity. From binding studies, the dissociation constant (K d) for amitrole with lactoperoxidase was found to be approximately 5.5 × 10−7 M, indicating high affinity.
Keywords: Antimicrobial activity; Heme; Oxidation; Peroxidase; Crystal structure; Distal heme cavity
Aromatic C–H bond hydroxylation by P450 peroxygenases: a facile colorimetric assay for monooxygenation activities of enzymes based on Russig’s blue formation by Osami Shoji; Christian Wiese; Takashi Fujishiro; Chikako Shirataki; Bernhard Wünsch; Yoshihito Watanabe (1109-1115).
Aromatic C–H bond hydroxylation of 1-methoxynaphthalene was efficiently catalyzed by the substrate misrecognition system of the hydrogen peroxide dependent cytochrome P450BSβ (CYP152A1), which usually catalyzes hydroxylation of long-alkyl-chain fatty acids. Very importantly, the hydroxylation of 1-methoxynaphthalene can be monitored by a color change since the formation of 4-methoxy-1-naphthol was immediately followed by its further oxidation to yield Russig’s blue. Russig’s blue formation allows us to estimate the peroxygenation activity of enzymes without the use of high performance liquid chromatography, gas chromatography, and nuclear magnetic resonance measurements.
Keywords: Cytochrome P450; Hydroxylation; Hydrogen peroxide; Colorimetric assay; Enzyme catalysis
Spectroscopic insights into axial ligation and active-site H-bonding in substrate-bound human heme oxygenase-2 by Jessica D. Gardner; Li Yi; Stephen W. Ragsdale; Thomas C. Brunold (1117-1127).
Heme oxygenases (HOs) are monooxygenases that catalyze the first step in heme degradation, converting heme to biliverdin with concomitant release of Fe(II) and CO from the porphyrin macrocycle. Two heme oxygenase isoforms, HO-1 and HO-2, exist that differ in several ways, including a complete lack of Cys residues in HO-1 and the presence of three Cys residues as part of heme-regulatory motifs (HRMs) in HO-2. HRMs in other heme proteins are thought to directly bind heme, or to otherwise regulate protein stability or activity; however, it is not currently known how the HRMs exert these effects on HO-2 function. To better understand the properties of this vital enzyme and to elucidate possible roles of its HRMs, various forms of HO-2 possessing distinct alterations to the HRMs were prepared. In this study, variants with Cys265 in a thiol form are compared with those with this residue in an oxidized (part of a disulfide bond or existing as a sulfenate moiety) form. Absorption and magnetic circular dichroism spectroscopic data of these HO-2 variants clearly demonstrate that a new low-spin Fe(III) heme species characteristic of thiolate ligation is formed when Cys265 is reduced. Additionally, absorption, magnetic circular dichroism, and resonance Raman data collected at different temperatures reveal an intriguing temperature dependence of the iron spin state in the heme–HO-2 complex. These findings are consistent with the presence of a hydrogen-bonding network at the heme’s distal side within the active site of HO-2 with potentially significant differences from that observed in HO-1.
Keywords: Heme oxygenase; Heme; Magnetic circular dichroism; Resonance Raman
Complex formation and stability of westiellamide derivatives with copper(II) by Peter Comba; Nina Dovalil; Gebhard Haberhauer; Graeme R. Hanson; Yuki Kato; Toshiaki Taura (1129-1135).
The CuII coordination chemistry of three synthetic analogues of westiellamide (H3Lwa) with an azacrown-6 macrocyclic structure and imidazole (H3L1), oxazole (H3L2), or thiazole (H3L3) heterocyclic donors in addition to the peptide groups, is reported. The Nheterocycle–Npeptide–Nheterocycle binding sites are highly preorganized for the coordination to CuII ions. The stability constants of mono- and dinuclear CuII complexes of H3L1, H3L2, and H3L3, obtained by isothermal titration microcalorimetry, are reported. EPR and NMR spectroscopy as well as electrospray ionization mass spectrometry (ESI-MS) were used to characterize the complexes formed in solution. The stabilities of the mononuclear and dinuclear CuII complexes of the three ligands are in the range of 105 M−1, but there are subtle differences; specifically the oxazole-derived ligand has, in contrast to the other two macrocycles, a negative formation entropy for coordination to the first CuII ion and a higher stability for complexation to a second CuII center in comparison with the first CuII center (cooperativity). Differences between the three ligands are also apparent in terms of the formation mechanism. With the oxazole-based ligand H3L2, NMR spectroscopy, EPR spectroscopy, and ESI-MS indicate the formation of a ligand–CuII 2:1 intermediate, and this may explain the differences in the formation entropy as well as the cooperativity.
Keywords: Cyclic peptides; Stability constants; Complex formation; Spectroscopy; Westiellamide
Dynamic accumulation and redistribution of methylmercury in the lens of developing zebrafish embryos and larvae by Malgorzata Korbas; Patrick H. Krone; Ingrid J. Pickering; Graham N. George (1137-1145).
Neurotoxic methylmercury compounds are widespread in the environment and human exposure worries many communities worldwide. Despite numerous studies addressing methylmercury toxicity, the detailed mechanisms underlying its transport and accumulation, especially during early developmental stages, remain unclear. Zebrafish larvae are increasingly used as a model system for studies of vertebrate development and toxicology. Previously, we have identified the lens epithelium as the primary site for cellular mercury accumulation in developing zebrafish larvae (Korbas et al. in Proc Natl Acad Sci USA 105:12108–12112, 2008). Here we present a study on the dynamics of methylmercury accumulation and redistribution in the lens following embryonic and larval exposure to methylmercury l-cysteineate using synchrotron X-ray fluorescence imaging. We observed highly specific accumulation of mercury in the lens that continues well after removal of fish from treatment solutions, thus significantly increasing the post-exposure loading of mercury in the lens. The results indicate that mercury is redistributed from the original target tissue to the eye lens, identifying the developing lens as a major sink for methylmercury in early embryonic and larval stages.
Keywords: Methylmercury; Zebrafish; X-ray fluorescence imaging; Lens
Correlation of concentrations of selected trace elements with Gleason grade of prostate tissues by A. Banas; W. M. Kwiatek; K. Banas; M. Gajda; B. Pawlicki; T. Cichocki (1147-1155).
The causes of prostate cancer are still obscure but some evidence indicates that there is a close connection between several trace elements and processes which may lead to malignant cells. In our study the microbeam synchrotron radiation X-ray fluorescence emission (micro-SRIXE) technique was applied for quantitative analysis of selected elements. For the first time, we correlate the concentrations of Mn, Fe, Cu, and Zn with the clinical stage of the prostate cancer at the time of operation (described by Gleason grade). Serial sections of prostate tissues were collected from patients undergoing radical prostatectomy. One section, stained with hematoxylin and eosin, was prepared for histopathological analysis; a second, adjacent unstained section was used in micro-SRIXE experiments. All experiments were performed at beamline L at HASYLAB, DESY, Germany. Our results seem to be valuable in light of the determination of the changes in the concentrations of trace elements as a potential diagnostic marker and their etiological involvement in the different stages of prostate diseases.
Keywords: Trace elements; Prostate cancer; Gleason grade; Microbeam synchrotron radiation X-ray fluorescence emission
Antiproliferative Pt(IV) complexes: synthesis, biological activity, and quantitative structure–activity relationship modeling by Paola Gramatica; Ester Papa; Mara Luini; Elena Monti; Marzia B. Gariboldi; Mauro Ravera; Elisabetta Gabano; Luca Gaviglio; Domenico Osella (1157-1169).
Several Pt(IV) complexes of the general formula [Pt(L)2(L′)2(L″)2] [axial ligands L are Cl−, RCOO−, or OH−; equatorial ligands L′ are two am(m)ine or one diamine; and equatorial ligands L″ are Cl− or glycolato] were rationally designed and synthesized in the attempt to develop a predictive quantitative structure–activity relationship (QSAR) model. Numerous theoretical molecular descriptors were used alongside physicochemical data (i.e., reduction peak potential, E p, and partition coefficient, log P o/w) to obtain a validated QSAR between in vitro cytotoxicity (half maximal inhibitory concentrations, IC50, on A2780 ovarian and HCT116 colon carcinoma cell lines) and some features of Pt(IV) complexes. In the resulting best models, a lipophilic descriptor (log P o/w or the number of secondary sp 3 carbon atoms) plus an electronic descriptor (E p, the number of oxygen atoms, or the topological polar surface area expressed as the N,O polar contribution) is necessary for modeling, supporting the general finding that the biological behavior of Pt(IV) complexes can be rationalized on the basis of their cellular uptake, the Pt(IV) → Pt(II) reduction, and the structure of the corresponding Pt(II) metabolites. Novel compounds were synthesized on the basis of their predicted cytotoxicity in the preliminary QSAR model, and were experimentally tested. A final QSAR model, based solely on theoretical molecular descriptors to ensure its general applicability, is proposed.
Keywords: Platinum complexes; Anticancer drug; Cytotoxicity; Quantitative structure–activity relationship analysis
Erratum to: Aromatic C–H bond hydroxylation by P450 peroxygenases: a facile colorimetric assay for monooxygenation activities of enzymes based on Russig’s blue formation by Osami Shoji; Christian Wiese; Takashi Fujishiro; Chikako Shirataki; Bernhard Wünsch; Yoshihito Watanabe (1171-1171).
A note from the President (1173-1173).