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1.
Front Chem ; 10: 976635, 2022.
Article in English | MEDLINE | ID: mdl-36092655

ABSTRACT

Flerovium (Fl, element 114) is the heaviest element chemically studied so far. To date, its interaction with gold was investigated in two gas-solid chromatography experiments, which reported two different types of interaction, however, each based on the level of a few registered atoms only. Whereas noble-gas-like properties were suggested from the first experiment, the second one pointed at a volatile-metal-like character. Here, we present further experimental data on adsorption studies of Fl on silicon oxide and gold surfaces, accounting for the inhomogeneous nature of the surface, as it was used in the experiment and analyzed as part of the reported studies. We confirm that Fl is highly volatile and the least reactive member of group 14. Our experimental observations suggest that Fl exhibits lower reactivity towards Au than the volatile metal Hg, but higher reactivity than the noble gas Rn.

2.
Front Chem ; 9: 753738, 2021.
Article in English | MEDLINE | ID: mdl-34917588

ABSTRACT

Nihonium (Nh, element 113) and flerovium (Fl, element 114) are the first superheavy elements in which the 7p shell is occupied. High volatility and inertness were predicted for Fl due to the strong relativistic stabilization of the closed 7p 1/2 sub-shell, which originates from a large spin-orbit splitting between the 7p 1/2 and 7p 3/2 orbitals. One unpaired electron in the outermost 7p 1/2 sub-shell in Nh is expected to give rise to a higher chemical reactivity. Theoretical predictions of Nh reactivity are discussed, along with results of the first experimental attempts to study Nh chemistry in the gas phase. The experimental observations verify a higher chemical reactivity of Nh atoms compared to its neighbor Fl and call for the development of advanced setups. First tests of a newly developed detection device miniCOMPACT with highly reactive Fr isotopes assure that effective chemical studies of Nh are within reach.

3.
Cytokine ; 148: 155665, 2021 12.
Article in English | MEDLINE | ID: mdl-34366205

ABSTRACT

The pro-inflammatory IFNγ-STAT1 pathway and anti-inflammatory IL10-STAT3 pathway elicit cellular responses primarily utilizing their canonical STATs. However IL10 mediated STAT1 and IFNγ mediated STAT3 activation is also observed, suggesting crosstalk of these functionally opposing signaling pathways can potentially reshape the canonical dynamics both STATs and alter the expression of their target genes. Herein, we measured the dynamics of STATs in response to different doses of IL10 or IFNγ and in their co-stimulation and employed quantitative modeling to understand the regulatory mechanisms controlling signal responses in individual and co-simulation scenarios. Our experiments show, STAT3 in particular, exhibits a bell-shaped dose-response while treated with IFNγ or IL10 and our model quantiatively captured the dose-dependent dynamics of both the STATs in both pathways. The model next predicted and subsequent experiments validated that STAT3 dynamics would robustly remain IL10 specific when subjected to a co-stimulation of both IFNγ and IL10. Genes common to both pathways also exhibited IL10 specific expression during the co-stimulation. The findings thus uncover anovel feature of the IL10-STAT3 signaling axis during pathway crosstalk. Finally, parameter sampling coupled to information theory based analysis showed that bell-shaped signal-response of STAT3 in both pathways is primarily dependent on receptor concentration whereas robustness of IL10-STAT3 signaling axis in co-stimulation results from the negative regulation of the IFNγ pathway.


Subject(s)
Interferon-gamma/pharmacology , Interleukin-10/pharmacology , Signal Transduction , Suppressor of Cytokine Signaling 3 Protein/metabolism , Animals , Calibration , Gene Expression Regulation/drug effects , Humans , Mice, Inbred BALB C , Models, Biological , Phosphorylation/drug effects , Reproducibility of Results , STAT1 Transcription Factor/metabolism
4.
J Phys Condens Matter ; 32(40): 405301, 2020 Jul 08.
Article in English | MEDLINE | ID: mdl-32639952

ABSTRACT

We study the transport properties of junctions of normal and superconducting Weyl semimetal with tilted dispersion, in the presence of magnetization induced by magnetic strips. The sub gap tunnelling conductance shows robust signatures in the presence of different orientation and strength of magnetization of the magnetic strips. We obtain the analytical results for the normal-magnetic-superconducting junction in the thin barrier limit and demonstrate that these results have no analogues to their conventional counterparts and junctions with Dirac electrons in two-dimensions. We discuss possible experimental setups to test our theoretical predictions.

5.
Math Biosci ; 282: 46-60, 2016 12.
Article in English | MEDLINE | ID: mdl-27702638

ABSTRACT

Japanese encephalitis (JE) is a public health problem that threats the entire world today. Japanese Encephalitis virus (JEV) mostly became a threat due to the significant number of increase of susceptible mosquito vectors and vertebrate hosts in Asia by which around 70,000 cases and 10,000 deaths per year took place in children below 15 years of age. In this paper, a mathematical model of JE due to JEV from the vector source (infected mosquito) and two vertebrate hosts (infected human and infected pig) is formulated. The disease can be controlled by applying several control measures such as vaccination, medicine and insecticide to the JE infection causing species. The model has been formulated as an optimal control problem and has been solved using Pontryagin's maximum principle. Also, the stability of the system has been studied with the help of basic reproduction number for disease free and endemic equilibrium. The results of fixed control for endemic equilibrium is presented numerically and depicted graphically. The effects of different control strategies on human, pig and mosquito has been analyzed using Runge-Kutta 4th order forward and backward techniques and presented thereafter graphically.


Subject(s)
Basic Reproduction Number , Communicable Disease Control/methods , Encephalitis, Japanese/prevention & control , Models, Theoretical , Animals , Culicidae , Humans , Swine
6.
Phys Rev Lett ; 115(24): 242502, 2015 Dec 11.
Article in English | MEDLINE | ID: mdl-26705628

ABSTRACT

Two short-lived isotopes ^{221}U and ^{222}U were produced as evaporation residues in the fusion reaction ^{50}Ti+^{176}Yb at the gas-filled recoil separator TASCA. An α decay with an energy of E_{α}=9.31(5) MeV and half-life T_{1/2}=4.7(7) µs was attributed to ^{222}U. The new isotope ^{221}U was identified in α-decay chains starting with E_{α}=9.71(5) MeV and T_{1/2}=0.66(14) µs leading to known daughters. Synthesis and detection of these unstable heavy nuclei and their descendants were achieved thanks to a fast data readout system. The evolution of the N=126 shell closure and its influence on the stability of uranium isotopes are discussed within the framework of α-decay reduced width.

7.
Phys Rev Lett ; 112(17): 172501, 2014 May 02.
Article in English | MEDLINE | ID: mdl-24836239

ABSTRACT

The superheavy element with atomic number Z=117 was produced as an evaporation residue in the (48)Ca+(249)Bk fusion reaction at the gas-filled recoil separator TASCA at GSI Darmstadt, Germany. The radioactive decay of evaporation residues and their α-decay products was studied using a detection setup that allowed measuring decays of single atomic nuclei with half-lives between sub-µs and a few days. Two decay chains comprising seven α decays and a spontaneous fission each were identified and are assigned to the isotope (294)117 and its decay products. A hitherto unknown α-decay branch in (270)Db (Z = 105) was observed, which populated the new isotope (266)Lr (Z = 103). The identification of the long-lived (T(1/2) = 1.0(-0.4)(+1.9) h) α-emitter (270)Db marks an important step towards the observation of even more long-lived nuclei of superheavy elements located on an "island of stability."

8.
J Appl Microbiol ; 114(5): 1357-68, 2013 May.
Article in English | MEDLINE | ID: mdl-23311514

ABSTRACT

AIM: To characterize a new isolate of Candida tropicalis for its enhanced storage lipid accumulation with respect to lipid composition, fatty acid profile and transcriptional regulation of four key genes involved in lipid productivity using different carbon sources. METHODS AND RESULTS: Upon growing C. tropicalis on various carbon substrates, glucose was found to be the best followed by xylose for the production of both biomass and storage lipid. On glucose (100 g l(-1)) medium having specific nitrogen stress (C:N 150 : 1), the yeast was capable of yielding about 58% lipid content of its dry biomass, and neutral lipid accounted for about 75% of the total lipid. Fatty acid profiles revealed that the glucose contributed to the highest yield of total fatty acids, maximum proportion of saturated fatty acids and a significant amount of oleic acid. The enhanced lipid production with specific fatty acid profile correlated with the strong upregulation of acetyl Co-A carboxylase, stearoyl-ACP desaturase and diacylglycerol acyltransferase genes, but not the malic enzyme gene. CONCLUSIONS: Together, the results documented the differential regulation of four genes of lipid biosynthesis in the newly isolated C. tropicalis oleaginous strain by various carbon sources. SIGNIFICANCE AND IMPACT OF THE STUDY: We report here on optimization of the carbon substrate for improved lipid yield and transcriptional regulation of lipid biosynthetic genes in C. tropicalis. Our study paves the way for further enhancement of lipid production by metabolic engineering in this organism, which has potential to be the lipid feedstock as a cocoa-butter substitute.


Subject(s)
Candida tropicalis/metabolism , Carbon/metabolism , Lipids/biosynthesis , Acetyl-CoA Carboxylase/genetics , Biomass , Candida tropicalis/genetics , Candida tropicalis/isolation & purification , Culture Media/chemistry , Diacylglycerol O-Acyltransferase/genetics , Fatty Acids/biosynthesis , Gene Expression Regulation, Fungal , Glucose/metabolism , Industrial Microbiology , Malate Dehydrogenase/genetics , Mixed Function Oxygenases/genetics , Nitrogen/metabolism , Oleic Acid/biosynthesis , RNA, Ribosomal/genetics , Soil Microbiology , Transcriptome , Xylose/metabolism
9.
Phys Rev Lett ; 104(25): 252701, 2010 Jun 25.
Article in English | MEDLINE | ID: mdl-20867370

ABSTRACT

The fusion-evaporation reaction 244Pu(48Ca,3-4n){288,289}114 was studied at the new gas-filled recoil separator TASCA. Thirteen correlated decay chains were observed and assigned to the production and decay of {288,289}114. At a compound nucleus excitation energy of E{*}=39.8-43.9 MeV, the 4n evaporation channel cross section was 9.8{-3.1}{+3.9} pb. At E^{*}=36.1-39.5 MeV, that of the 3n evaporation channel was 8.0{-4.5}{+7.4} pb. In one of the 3n evaporation channel decay chains, a previously unobserved α branch in 281Ds was observed (probability to be of random origin from background: 0.1%). This α decay populated the new nucleus 277Hs, which decayed by spontaneous fission after a lifetime of 4.5 ms.

10.
Eur Phys J E Soft Matter ; 32(2): 217-21, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20571848

ABSTRACT

We study the thermodynamic and kinetic consequences of the competition between single-protein folding and protein-protein aggregation using a phenomenological model, in which the proteins can be in the unfolded (U), misfolded (M) or folded (F) states. The phase diagram shows the coexistence between a phase with aggregates of misfolded proteins and a phase of isolated proteins (U or F) in solution. The spinodal at low protein concentrations shows non-monotonic behavior with temperature, with implications for the stability of solutions of folded proteins at low temperatures. We follow the dynamics upon "quenching" from the U-phase (cooling) or the F-phase (heating) to the metastable or unstable part of the phase diagram that results in aggregation. We describe how interesting consequences to the distribution of aggregate size, and growth kinetics arise from the competition between folding and aggregation.


Subject(s)
Models, Molecular , Protein Folding , Protein Multimerization , Proteins/chemistry , Proteins/metabolism , Kinetics , Models, Biological , Protein Denaturation , Protein Structure, Quaternary , Solutions , Thermodynamics
11.
Bioresour Technol ; 101(17): 6843-51, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20395134

ABSTRACT

In this paper, corn starch based green composites reinforced with graft copolymers of Saccharum spontaneum L. (Ss) fiber and methyl methacrylates (MMA) and its mixture with acrylamide (AAm), acrylonitrile (AN), acrylic acid (AA) were prepared. Resorcinol-formaldehyde (Rf) was used as the cross-linking agent in corn starch matrix and different physico-chemical, thermal and mechanical properties were evaluated. The matrix and composites were found to be thermally more stable than the natural corn starch backbone. Further the matrix and composites were subjected for biodegradation studies through soil composting method. Different stages of biodegradation were evaluated through FT-IR and scanning electron microscopic (SEM) techniques. S. spontaneum L fiber-reinforced composites were found to exhibit better tensile strength. On the other hand Ss-g-poly (MMA) reinforced composites showed maximum compressive strength and wear resistance than other graft copolymers reinforced composite and the basic matrix.


Subject(s)
Polymers/chemistry , Saccharum/chemistry , Starch/chemistry , Zea mays/chemistry , Microscopy, Electron, Scanning , Spectroscopy, Fourier Transform Infrared , Tensile Strength
12.
Radiat Prot Dosimetry ; 136(2): 67-73, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19700498

ABSTRACT

Ambient neutron dose equivalent from 20 MeV protons incident on thick Be and Cu targets are measured at 0 degrees, 30 degrees, 60 degrees and 90 degrees with respect to the beam direction using a conventional dose equivalent meter. The neutron spectra calculated using nuclear reaction model codes ALICE, PRECO and earlier reported empirical expressions are converted to the ambient dose equivalent using the ICRP fluence-to-dose conversion coefficients and are compared with the measured values. The experimental energy spectra reported in the literature for 19.08 MeV protons incident on a thick Be target are also converted to ambient neutron dose equivalent and are compared with the present experimental results. It is observed that the values estimated from the neutron spectra obtained from the nuclear reaction codes are unable to predict the measured values. The results obtained from the reported experimental energy spectra compare well with the results obtained here. An empirical relation that was used to calculate the directional dependence of the measured neutron dose equivalent from heavy ion-induced reactions is used in this study to check its effectiveness for proton-induced reactions.


Subject(s)
Beryllium , Copper , Neutrons , Protons , Radiation Dosage
13.
Radiat Prot Dosimetry ; 123(3): 277-82, 2007.
Article in English | MEDLINE | ID: mdl-16987909

ABSTRACT

Measured angular distribution of neutron dose from 110 MeV (19)F projectiles bombarding a thick aluminium target is reported. The measurements are carried out with a commercially available rem meter at 0 degrees, 30 degrees, 60 degrees and 90 degrees. The experimental results are compared with calculated dose from different empirical formulations proposed by earlier workers as well as with calculated dose from theoretically estimated energy distributions from the nuclear reaction model code EMPIRE-2.18.


Subject(s)
Algorithms , Aluminum/chemistry , Fluorine/chemistry , Models, Chemical , Neutrons , Radiometry/methods , Computer Simulation , Energy Transfer , Radiation Dosage , Reproducibility of Results , Sensitivity and Specificity
14.
Plant Physiol Biochem ; 44(11-12): 645-55, 2006.
Article in English | MEDLINE | ID: mdl-17092734

ABSTRACT

A cDNA of fatty acyl-acyl carrier protein (ACP) thioesterase (Fat) from developing seed of Madhuca butyracea has been cloned. The deduced amino acid sequence of the cDNA corresponding to the mature polypeptide showed 30-40% and 60-75% identity to the reported FatA and FatB class of plant thioesterases, respectively. This gene, MbFatB, is present as a single copy in M. butyracea genome and the MbFatB protein was detected clearly in seed tissues of this plant but not in that of Indian mustard (Brassica juncea). Heterologous expression of the MbFatB gene driven by different promoters in E. coli wild type and fatty acid beta-oxidation mutant (fadD88) strains resulted production of the recombinant protein with various fusion tags either as biologically inactive (insoluble) or functionally active forms. Expression of functionally active recombinant MbFatB in E. coli affected bacterial growth and cell morphology as well as changed the fatty acid profiles of the membrane lipid and the culture supernatant. Alteration of the fatty acid composition was directed predominantly towards palmitate and to a lesser extent myristate and oleate due to acyl chain termination activity of plant thioesterase in bacteria. Thus, this new MbFatB gene isolated from a non-traditional oil-seed tree can be used in future for transgenic development of oil-seed Brassica, a widely cultivated crop that expresses predominantly oleoyl-ACP thioesterase (FatA) in its seed tissue and has high amount of unwanted erucic acid in edible oil in order to alter the fatty acid profile in a desirable way.


Subject(s)
Genome, Plant , Madhuca/genetics , Plant Proteins/genetics , Thiolester Hydrolases/genetics , Amino Acid Sequence , Cloning, Molecular , Escherichia coli/genetics , Gene Expression , Madhuca/enzymology , Molecular Sequence Data , Plant Proteins/metabolism , Recombinant Proteins/biosynthesis , Recombinant Proteins/genetics , Seeds/enzymology , Seeds/genetics , Thiolester Hydrolases/biosynthesis
15.
Article in English | MEDLINE | ID: mdl-12524123

ABSTRACT

Both steady state and time resolved spectroscopic measurements reveal that the prime process involved in quenching mechanism of the lowest excited singlet (S1) and triplet (T1) states of the well known electron acceptor 9-Cyanoanthracene (9CNA) in presence of 5,6,7,8-tetrahydro-1-naphthol (TH1N) or 5,6,7,8-tetrahydro-2-naphthol (TH2N) is H-bonding interaction. It has been confirmed that the fluorescence of 9CNA is not at all affected in presence of 5,6,7,8-tetrahydro-2-methoxy naphthalene (TH2MN) both in non-polar n-heptane (NH) and highly polar acetonitrile (ACN) media. This indicates that the H-bonding interaction is crucial for the occurrence of the quenching phenomenon observed in the present investigations with TH1N (or TH2N) donors and 9CNA acceptor. In ACN solvent both contact ion-pair (CIP) and solvent-separated (or dissociated) ions are formed due to intermolecular H-bonding interactions in the excited electronic states (both singlet and triplet). In NH environment due to stronger H-bonding interactions, the large proton shift within excited charge transfer (CT) or ion-pair complex, 1 or 3(D+-H...A-), causes the formation of the neutral radical, 3(D+H-A)*, due to the complete detachment of the H-atom. It is hinted that both TH1N and TH2N due to their excellent H-bonding ability could be used as antioxidants.


Subject(s)
Anthracenes/chemistry , Naphthols/chemistry , Electrochemistry , Electron Transport , Hydrogen Bonding , Photochemistry , Photolysis , Spectrometry, Fluorescence , Spectrophotometry
16.
Spectrochim Acta A Mol Biomol Spectrosc ; 58(8): 1631-41, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12166735

ABSTRACT

By using steady state and time-resolved (laser flash photolysis and single photon counting) spectroscopic techniques the quenching of the lowest excited singlet (S1) state of 9-cyanoanthracene (9CNA) by the donors (quenchers) 2-methylindole (2MI) and 2-methylindoline (2MIN) in solvents of different polarity has been studied. Both the transient absorption, by laser flash photolysis technique, and photobleaching measurements were made at the ambient temperature both in non-polar n-heptane (NH) and highly polar acetonitrile (ACN) solvents. The photobleaching efficiency (alpha) was found to depend significantly on the polarity of surrounding solvents and also on the molecular structures of the quenchers. In NH the values of alpha are found to be larger than the corresponding values observed in ACN for both 2MI and 2MIN which possess highly reactive H atom bound to the heterocyclic N atom. Following the results obtained from the transient absorption spectra of the present donor-acceptor molecules in the different polarity solvents, a scheme describing the overall reaction mechanisms of the different photoreactions involved has been proposed. The probable causes for the changes observed in the mechanisms of the photoreactions involved in the cases of 2MI and 2MIN donors have been discussed in the light of their canonical structures.


Subject(s)
Anthracenes/chemistry , Indoles/chemistry , Cyanides/chemistry , Electrochemistry , Lasers , Photobleaching , Photochemistry , Photolysis , Solvents , Spectrometry, Fluorescence , Spectrophotometry
17.
Indian J Biochem Biophys ; 39(2): 106-12, 2002 Apr.
Article in English | MEDLINE | ID: mdl-22896897

ABSTRACT

Interaction of sanguinarine with A-form RNA structures of poly(rI)poly(rC) and poly(rA).poly(rU) has been studied by spectrophotometric, spectrofluorimetric, UV melting profiles, circular dichroism and viscometric analysis. The binding of sanguinarine to A-form duplex RNA structures is characterised by the typical bathochromic and hypochromic effects in the absorption spectrum, increasing steady state fluorescence intensity, an increase in fluorescence quantum yield of sanguinarine, an increase in fluorescence polarization anisotropy, an increase of thermal transition temperature, an increase in the contour length of sonicated rod-like RNA structure and perturbation in circular dichroic spectrum. Scatchard analysis indicates that sanguinarine binds to each polymer in a non-cooperative manner. Comparative binding parameters determined from absorbance titration by Scatchard analysis, employing the excluded site model, indicate a higher binding affinity of sanguinarine to poly(rI).poly(rC) structure than to poly(rA).poly(rU) structure. On the basis of these observations, it is concluded that the alkaloid binds to both the RNA structures by a mechanism of intercalation.


Subject(s)
Benzophenanthridines/chemistry , Isoquinolines/chemistry , RNA, Double-Stranded/chemistry , Anisotropy , Anti-Infective Agents/chemistry , Circular Dichroism/methods , Hydrodynamics , Kinetics , Microscopy, Fluorescence/methods , Models, Chemical , Molecular Conformation , Protein Binding , Spectrophotometry/methods , Viscosity
18.
Indian J Biochem Biophys ; 38(1-2): 20-6, 2001.
Article in English | MEDLINE | ID: mdl-11563326

ABSTRACT

The interaction of sanguinarine with right-handed (B-form), left-handed (Z-form) and left-handed (HL-form) structures of poly(dG-dC).poly(dG-dC) has been investigated by measuring the circular dichroism (CD) and UV-absorption spectral analysis. Sanguinarine binds strongly to the B-form DNA and does not bind to Z-form or HL-form, but it converts the Z-form and the HL-form back to the bound right handed form as evidenced from CD spectroscopy. Sanguinarine inhibits the rate of B to Z transition under ionic conditions that otherwise favour the left-handed conformation of the polynucleotides. UV absorption kinetic studies show that the Z-form reverses back to B-form to B-form on binding to sanguinarine. Binding isotherms obtained from spectrophotometric data show that sanguinarine binds strongly to the B-form polymer in a non-cooperative manner, in sharp contrast to the highly cooperative interaction under Z-form and HL-form polynucleotides. These studies reveal that the alternating GC sequence undergoes defined conformational changes and interacts with sanguinarine which may be an important aspect in understanding its extensive biological activities.


Subject(s)
Alkaloids/pharmacology , DNA/chemistry , Hydrogen/chemistry , Intercalating Agents/pharmacology , Nucleic Acid Conformation , Benzophenanthridines , Circular Dichroism , Hydrogen Bonding , Isoquinolines , Kinetics , Models, Chemical , Spectrophotometry , Time Factors
19.
Biochemistry ; 38(19): 6239-47, 1999 May 11.
Article in English | MEDLINE | ID: mdl-10320353

ABSTRACT

The interaction of aristololactam-beta-D-glucoside (ADG), a DNA intercalating alkaloid, with the DNA triplexes, poly(dT). poly(dA)xpoly(dT) and poly(dC).poly(dG)xpoly(dC+), and the RNA triplex poly(rU).poly(rA)xpoly(rU) was investigated by circular dichroic, UV melting profile, spectrophotometric, and spectrofluorimetric techniques. Comparative interaction with the corresponding Watson-Crick duplexes has also been examined under identical experimental conditions. Triplex formation has been confirmed from biphasic thermal melting profiles and analysis of temperature-dependent circular dichroic measurements. The binding of ADG to triplexes and duplexes is characterized by the typical hypochromic and bathochromic effects in the absorption spectrum, quenching of steady-state fluorescence intensity, a decrease in fluorescence quantum yield, an increase or decrease of thermal melting temperatures, and perturbation in the circular dichroic spectrum. Scatchard analysis indicates that ADG binds both to the triplexes and the duplexes in a noncooperative manner. Binding parameters obtained from spectrophotometric measurements are best fit by the neighbor exclusion model. The binding affinity of ADG to the DNA triplexes is substantially stronger than to the RNA triplex. Thermal melting study further indicates that ADG stabilizes the Hoogsteen base-paired third strand of the DNA triplexes whereas it destabilizes the same strand of RNA triplex but stabilizes its Watson-Crick strands. Comparative data reveal that ADG exhibits a stronger binding to the triple helical structures than to the respective double helical structures.


Subject(s)
Alkaloids/metabolism , Aristolochic Acids , DNA/metabolism , Glucosides/metabolism , RNA/metabolism , Alkaloids/chemistry , Alkaloids/pharmacology , Circular Dichroism , DNA/chemistry , Glucosides/chemistry , Glucosides/pharmacology , Magnoliopsida/chemistry , Nucleic Acid Conformation/drug effects , RNA/chemistry , Spectrometry, Fluorescence , Spectrum Analysis
20.
Biophys Chem ; 76(3): 199-218, 1999 Feb 22.
Article in English | MEDLINE | ID: mdl-17027465

ABSTRACT

The interaction of sanguinarine and ethidium with right-handed (B-form), left-handed (Z-form) and left-handed protonated (designated as H(L)-form) structures of poly(dG-dC).poly(dG-dC) and poly(dG-me5dC).poly(dG-me5dC) was investigated by measuring the circular dichroism and UV absorption spectral analysis. Both sanguinarine and ethidium bind strongly to the B-form DNA and convert the Z-form and the H(L)-form back to the bound right-handed form. Circular dichroic data also show that the conformation at the binding site is right-handed, even though adjacent regions of the polymer have a left-handed conformation either in Z-form or in H(L)-form. Both the rate and extent of B-form to Z-form transition were decreased by sanguinarine and ethidium under ionic conditions that otherwise favour the left-handed conformation of the polynucleotides. The rate of decrease is faster in the case of ethidium as compared to that of sanguinarine. Scatchard analysis of the spectrophotometric data shows that sanguinarine binds strongly to both the polynucleotides in a non-cooperative manner under B-form conditions, in sharp contrast to the highly-cooperative binding under Z-form and H(L)-form conditions. Correlation of binding isotherms with circular dichroism data indicates that the cooperative binding of sanguinarine under the Z-form and the H(L)-form conditions is associated with a sequential conversion of the polymer from a left-handed to a bound right-handed conformation. Determination of bound alkaloid concentration by spectroscopic titration technique and the measurement of circular dichroic spectra have enabled us to calculate the number of base pairs of Z-form and H(L)-form that adopt a right-handed conformation for each bound alkaloid. Analysis reveals that 2-3 base pairs (bp) of Z-form of poly(dG-dC).poly(dG-dC) and poly(dG-me5dC).poly(dG-me5dC) switch to the right-handed form for each bound sanguinarine, while approximately same number of base pairs switch to the bound right-handed form in complexes with H(L)-form of these polynucleotides. Comparative binding analysis shows that ethidium also converts approximately 2 bp of Z-form or H(L)-form to bound right-handed form under same experimental conditions. Since sanguinarine binds preferentially to alternating GC sequences, which are capable of undergoing the B to Z or B to H(L) transition, these effects may be an important part in understanding its extensive biological activities.

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