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1.
(1) Little information exists on the role of clustered Hox genes in oligodendrocyte (OG) development. This study examines the expression profile of Hoxd1 and identifies a potential
downstream target in the OG lineage. (2) Immunocytochemical analysis of primary mixed glial cultures demonstrated Hoxd1 was
expressed throughout OG development. (3) A human myelin protein gene, myelin oligodendrocyte glycoprotein (MOG), was identified
as a putative downstream target of Hoxd1 through Genbank searches utilizing the Hoxd1 homeodomain consensus binding sequence.
(4) The dissociation coefficient constant (K
D) and dissociation rate constant (k
d) of the Hoxd1–MOG complex, determined using electrophoretic mobility shift assays (EMSAs), were estimated to be 1.9 × 10−7 M and 1.3 × 10−3 s−1, respectively. The DNA–Hoxd1 homeodomain complex had a half-life (t
1/2) of 15 min. (5) Mutational analysis of Hoxd1–MOG complexes revealed the binding affinity of M1 (with mutation from −10545′-TAAT-3′−1051 to TACT within the consensus binding site) and M2 (with mutation from -10545′-TAATTG-3′-1049 to TAATCC within the consensus binding site) probes to the MOG promoter was severely affected. Thus the TAATTG core of the
binding sequence appears important for Hoxd1 specificity. (6) Analysis of the involvement of TAAT sites adjacent to the consensus
sequence in Hoxd1 binding showed the binding affinity of the M3 probe was affected, but not as severely as the M1 and M2 probes.
These in vitro results suggest the TTTAATTGTA sequence is involved in Hoxd1 binding to the MOG promoter but neighboring TAAT
sites may also be needed. Thus, MOG may be a target of Hoxd1. 相似文献
2.
The activated sludge process (ASP) has high operational costs due to the need for aeration at dissolved O2 (DO) levels of ≥2 mg l−1 and high capital costs to construct large reactors due to a low organic loading [typically 1 kg chemical oxygen demand (COD) m−3 day−1]. A novel method for improving the energy use and treatment efficiency of the ASP via limited oxygenation (0.4 mg DO l−1) and high organic loading (6.2 kg COD m−3 day−1) is proposed based on a laboratory-scale ASP for ammonia-rich industrial wastewaters. The sludge blanket phenomenon and granulation
occurred simultaneously in the upflow microaerobic reactor. 相似文献
3.
Two zinc(II) terpyridine complexes Zn(atpy)2(PF6)2 (1) (atpy = 4′-p-N9′-adeninylmethylphenyl-2,2′:6,2′′-terpyridine) and Zn(ttpy)2(PF6)2 (2) (ttpy = 4′-p-tolyl-2,2′:6,2′′-terpyridine) have been synthesized and characterized by elemental analysis, 1H NMR and electrospray mass spectroscopy. The structure of complex 2 was also determined by X-ray crystallography, which revealed a ZnN6 coordination in an octahedral geometry with two terpyridine acting as equatorial ligands. The circular dichroism data showed
that complex 1 exhibited an ICD signal at around 300 nm and induced more evident disturbances on DNA base stacking than complex 2, reflecting the impact of the adenine moiety on DNA binding modes. Complex 1 exhibited higher cleavage activity to supercoiled pUC 19 DNA than complex 2 under aerobic conditions, suggesting a promotional effect of adenine moiety in DNA nuclease ability. Interestingly, both
complexes demonstrated potent in vitro cytotoxicity against a series human tumor cell lines such as human cervix carcinoma
cell line (HeLa), human liver carcinoma cell line (HepG2), human galactophore carcinoma cell line (MCF-7) and human prostate
carcinoma cell line (pc-3). The cytotoxicity is averagely 10 times more active than the anticancer drug cisplatin.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
4.
Yanmei Duan Na Li Chao Liu Huiting Liu Yaling Cui Han Wang Fashui Hong 《Biological trace element research》2010,136(3):302-313
In order to study the mechanisms underlying the effects of TiO2 nanoparticles on lactate dehydrogenase (LDH, EC1.1.1.27), Institute of Cancer Research region mice were injected with nanoparticulate
anatase TiO2 (5 nm) of various doses into the abdominal cavity daily for 14 days. We then examined LDH activity in vivo and in vitro and
direct evident for interaction between nanoparticulate anatase TiO2 and LDH using spectral methods. The results showed that nanoparticulate anatase TiO2 could significantly activate LDH in vivo and in vitro; the kinetics constant (Km) and Vmax were 0.006 μM and 1,149 unit mg−1 protein min−1, respectively, at a low concentration of nanoparticulate anatase TiO2, and 3.45 and 0.031 μM and 221 unit mg−1 protein min−1, respectively, at a high concentration of nanoparticulate anatase TiO2. By fluorescence spectral assays, the nanoparticulate anatase TiO2 was determined to be directly bound to LDH, and the binding constants of the binding site were 1.77 × 108 L mol−1 and 2.15 × 107 L mol−1, respectively, and the binding distance between nanoparticulate anatase TiO2 and the Trp residue of LDH was 4.18 nm, and nanoparticulate anatase TiO2 induced the protein unfolding. It was concluded that the binding of nanoparticulate anatase TiO2 altered LDH structure and function. 相似文献
5.
Methane in the Changjiang (Yangtze River) Estuary and its adjacent marine area: riverine input,sediment release and atmospheric fluxes 总被引:7,自引:0,他引:7
Dissolved methane (CH4) was measured in the waters of the Changjiang (Yangtze River) Estuary and its adjacent marine area during five surveys from
2002 to 2006. Dissolved CH4 concentrations ranged from 2.71 to 89.2 nM and had seasonal variation with the highest values occurring in summer and lowest
in autumn. The horizontal distribution of dissolved CH4 decreased along the freshwater plume from the river mouth to the open sea. Dissolved CH4 in surface waters of the Changjiang was observed monthly at the most downstream main channel station Xuliujing (121o2′E,
31o46′N), which ranged from 16.2 to 126.2 nM with an average of 71.6 ± 36.3 nM. The average annual input of CH4 from the Changjiang to the Estuary and its adjacent area was estimated to be 2.24 mol s−1 equal to 70.6 × 106 mol year−1. Mean CH4 emission rate from the sediments of the Changjiang Estuary in spring was 1.97 μmol m−2 day−1, but it may be higher in summer due to hypoxia in the bottom waters and higher temperatures. The annual sea to air CH4 fluxes from the Changjiang Estuary and its adjacent marine area were estimated to be 61.4 ± 22.6 and 16.0 ± 6.1 μmol m−2 day−1, respectively, using three different gas exchange models. Hence the Changjiang Estuary and its adjacent marine area are net
sources of atmospheric CH4. 相似文献
6.
Part of the Larsen A Ice Shelf (64°15′S to 74°15′S) collapsed during January 1995. A first oceanographic and biological data
set from the newly free waters was obtained during December 1996. Typical shelf waters with temperatures near and below the
freezing point were found. A nutrient-rich water mass (max: PO4
3− 1.80 μmol L−1 and NO3
− 27.64 μmol L−1) was found between 70 and 200 m depth. Chlorophyll-a (Chl-a) values (max 14.24 μg L−1) were high; surface oxygen saturation ranged between 86 and 148%. Diatoms of the genera Nitzschia and Navicula and the prymnesiophyte Phaeocystis sp. were the most abundant taxa found. Mean daily primary production (Pc) estimated from nutrient consumption was 14.80 ± 0.17 mgC m−3 day−1. Pc was significantly correlated with total diatom abundance and Chl-a. Calculated ΔpCO2 (difference of the CO2 partial pressure between surface seawater and the atmosphere) was –30.5 μatm, which could have contributed to a net CO2 flux from the atmosphere to the sea and suggests the area has been a CO2 sink during the studied period. High phytoplankton biomass and production values were found in this freshly open area, suggesting
its importance for biological CO2 pumping. 相似文献
7.
Lina Wang Guanghong Ding Quanbao Gu Wolfgang Schwarz 《European biophysics journal : EBJ》2010,39(5):757-767
A stretch-activated (SA) Cl− channel in the plasma membrane of the human mast cell line HMC-1 was identified in outside-out patch-clamp experiments. SA
currents, induced by pressure applied to the pipette, exhibited voltage dependence with strong outward rectification (55.1 pS
at +100 mV and an about tenfold lower conductance at −100 mV). The probability of the SA channel being open (P
o) also showed steep outward rectification and pressure dependence. The open-time distribution was fitted with three components
with time constants of τ1o = 755.1 ms, τ2o = 166.4 ms, and τ3o = 16.5 ms at +60 mV. The closed-time distribution also required three components with time constants of τ1c = 661.6 ms, τ2c = 253.2 ms, and τ3c = 5.6 ms at +60 mV. Lowering extracellular Cl− concentration reduced the conductance, shifted the reversal potential toward chloride reversal potential, and decreased the
P
o at positive potentials. The SA Cl− currents were reversibly blocked by the chloride channel blocker 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS)
but not by (Z)-1-(p-dimethylaminoethoxyphenyl)-1,2-diphenyl-1-butene (tamoxifen). Furthermore, in HMC-1 cells swelling due to osmotic stress,
DIDS could inhibit the increase in intracellular [Ca2+] and degranulation. We conclude that in the HMC-1 cell line, the SA outward currents are mediated by Cl− influx. The SA Cl− channel might contribute to mast cell degranulation caused by mechanical stimuli or accelerate membrane fusion during the
degranulation process. 相似文献
8.
We investigated the effects of limiting (1.96 × 10−9 mol l−1 total Cu, corresponding to pCu 14.8; where pCu = −log [Cu2+]) and toxic Cu concentrations up to 8.0 × 10−5 mol l−1 total Cu (equivalent to pCu 9.5) on growth rates and photosynthetic activity of exponentially grown Phaeocystis cordata, using batch and semi-continuous cultures. With pulse amplitude modulated (PAM) fluorometry, we determined the photochemical
response of P. cordata to the various Cu levels, and showed contrasting results for the batch and semi-continuous cultures. Although maximum photosystem
II (PSII) quantum yield (ΦM) was optimal and constant in the semi-continuous P. cordata, the batch cultures showed a significant decrease in ΦM with culture age (0–72 h). The EC50 for the batch cultures was higher (2.0 × 10−10 mol l−1, pCu9.7), than that for the semi-continuous cultures (6.3 × 10−11 mol l−1, pCu10.2). The semi-continuous cultures exhibited a systematic and linear decrease in ΦM as Cu levels increased (for [Cu2+] < 1.0 × 10−12 mol l−1, pCu12.0), however, no effect of high Cu was observed on their operational PSII quantum yield (Φ′M). Similarly, semi-continuous cultures exhibited a significant decrease in ΦM, but not in Φ′M, because of low-Cu levels. Thus, Cu toxicity and Cu limitation damage the PSII reaction centers, but not the processes downstream
of PSII. Quenching mechanisms (NPQ and Q
n) were lower under high Cu relative to the controls, suggesting that toxic Cu impairs photo-protective mechanisms. PAM fluorometry
is a sensitive tool for detecting minor physiological variations. However, culturing techniques (batch vs. semi-continuous)
and sampling time might account for literature discrepancies on the effects of Cu on PSII. Semi-continuous culturing might
be the most adequate technique to investigate Cu effects on PSII photochemistry. 相似文献
9.
Joshua Otieno Ogweno Wen Hai Hu Xing Shun Song Kai Shi Wei Hua Mao Yan Hong Zhou Jing Quan Yu 《Plant Growth Regulation》2010,60(3):175-182
Detached leaves of tomato (Lycopersicon esculentum Mill.) experienced photoinhibition associated with sharp reductions in net photosynthetic rate (Pn), quantum efficiency of
PSII (ΦPSII) and photochemical quenching (qP) even though they were exposed to mild light intensity (400 μmol m−2 s−1 PPFD) at 28°C. Photoinhibition and the reduction in Pn, ΦPSII and qP, however, were significantly alleviated by 1 mg l−1 ABA, 0.1 mg l−1
N-(2-chloro-4-pyridyl)-N′-phenylurea (CPPU) and 0.01 mg l−1 24-epibrassinolide (EBR). Higher concentrations, however, reduced the effects or even exacerbated the occurrence of photoinhibition.
Superoxide dismutase and ascorbate peroxidase activity in leaves increased with the increases in ABA concentration within
1–100 mg l−1, CPPU concentration within 0.1–10 mg l−1 and EBR concentration within 0.01–1.0 mg l−1. Catalase and guaiacol peroxidase activity also increased with the increase in EBR concentration but CPPU and ABA treatments
at higher concentrations caused a decrease. Malondialdehyde (MDA) content decreased with the increase in CPPU concentration.
ABA and EBR, however, decreased MDA concentration only at 1 and 0.01 mg l−1, respectively. In conclusion, detached leaves had increased sensitivity to PSII photoinhibition. Photoinhibition-induced
decrease in photosynthesis, however, was significantly alleviated by EBR, CPPU and ABA at a proper concentration. 相似文献
10.
Gao E Guan F Gao X Zhu M Liu L Wang C Zhang W Sun Y 《Journal of biological inorganic chemistry》2012,17(2):263-274
Two novel palladium(II) complexes with a thiosalicylic acid (HSC6H4CO2H) ligand, with the formulas [Pd(TSA)(L)]·mH2O (TSA is thiosalicylic acid; in complex 1, L is 1,10-phenanthroline and m = 1; in complex 2, L is 2,2′-bipyridine and m = 2), have been synthesized and characterized. The coordination geometry of both palladium atoms is square planar; they are
four-coordinated and each is coordinated in an N,N,O−,S− mode. There is a sigmoid oxygen chain in complex 1, but an oxygen ring in complex 2. The competitive binding of the complexes to HeLa cell DNA (HL-DNA) has been investigated by fluorescence spectroscopy. The
results show that the two complexes have the ability to bind with HL-DNA. Viscosity studies suggest that the complexes bind
to DNA by intercalation. Gel electrophoresis assay demonstrated the ability of the complexes to cleave the HL-DNA. The two
complexes exhibit cytotoxic specificity and a significant cancer cell inhibitory rate. The apoptosis tests indicated that
the complexes have an apoptotic effect. Furthermore, complex 1 exhibits more biological activity than complex 2, which is mainly because the area of the aromatic ring of 1,10-phenanthroline is larger than that of 2,2′-bipyridine. 相似文献
11.
Felipe Zamborlini Saiter Frederico Augusto Guimarães Guilherme Luciana Dias Thomaz Tânia Wendt 《Biodiversity and Conservation》2011,20(9):1921-1949
The tree changes of 1.02 ha of montane forest at the Santa Lúcia Biological Station, southeastern Brazil, were analyzed using
two surveys separated by an interval of 11 years with the aim of confirming the patterns of stability of structure and diversity
over time. In the original survey all trees with diameter at breast height ≥6.4 cm were sampled. In second survey (this study),
dead trees, survivors and recruits in the same forest were reported. The data suggest a dynamic balance of the forest structure
because mortality (−1.06% year−1 for number of trees and −0.85% year−1 for basal area) was very close to recruitment (0.89% year−1) and ingrowth (1.05% year−1). The high diversity of the original survey (H′ > 5.2) was maintained by the turnover species. The main tree populations also showed stability of number of trees and basal
area. This pattern was shared by most of the 28 local endemic species, ensuring the maintenance of their populations in the
plot. 相似文献
12.
Merja R. Häkkinen Mervi T. Hyvönen Seppo Auriola Robert A. Casero Jr Jouko Vepsäläinen Alex R. Khomutov Leena Alhonen Tuomo A. Keinänen 《Amino acids》2010,38(2):369-381
N-alkylated polyamine analogues have potential as anticancer and antiparasitic drugs. However, their metabolism in the host
has remained incompletely defined thus potentially limiting their utility. Here, we have studied the degradation of three
different spermine analogues N,N′-bis-(3-ethylaminopropyl)butane-1,4-diamine (DESPM), N-(3-benzyl-aminopropyl)-N′-(3-ethylaminopropyl)butane-1,4-diamine (BnEtSPM) and N,N′-bis-(3-benzylaminopropyl)butane-1,4-diamine (DBSPM) and related mono-alkylated derivatives as substrates of recombinant
human polyamine oxidase (APAO) and spermine oxidase (SMO). APAO and SMO metabolized DESPM to EtSPD [K
m(APAO) = 10 μM, k
cat(APAO) = 1.1 s−1 and K
m(SMO) = 28 μM, k
cat(SMO) = 0.8 s−1, respectively], metabolized BnEtSPM to EtSPD [K
m(APAO) = 0.9 μM, k
cat(APAO) = 1.1 s−1 and K
m(SMO) = 51 μM, k
cat(SMO) = 0.4 s−1, respectively], and metabolized DBSPM to BnSPD [K
m(APAO) = 5.4 μM, k
cat(APAO) = 2.0 s−1 and K
m(SMO) = 33 μM, k
cat(SMO) = 0.3 s−1, respectively]. Interestingly, mono-alkylated spermine derivatives were metabolized by APAO and SMO to SPD [EtSPM K
m(APAO) = 16 μM, k
cat(APAO) = 1.5 s−1; K
m(SMO) = 25 μM, k
cat(SMO) = 8.2 s−1; BnSPM K
m(APAO) = 6.0 μM, k
cat(APAO) = 2.8 s−1; K
m(SMO) = 19 μM, k
cat(SMO) = 0.8 s−1, respectively]. Surprisingly, EtSPD [K
m(APAO) = 37 μM, k
cat(APAO) = 0.1 s−1; K
m(SMO) = 48 μM, k
cat(SMO) = 0.05 s−1] and BnSPD [K
m(APAO) = 2.5 μM, k
cat(APAO) = 3.5 s−1; K
m(SMO) = 60 μM, k
cat(SMO) = 0.54 s−1] were metabolized to SPD by both the oxidases. Furthermore, we studied the degradation of DESPM, BnEtSPM or DBSPM in the
DU145 prostate carcinoma cell line. The same major metabolites EtSPD and/or BnSPD were detected both in the culture medium
and intracellularly after 48 h of culture. Moreover, EtSPM and BnSPM were detected from cell samples. Present data shows that
inducible SMO parallel with APAO could play an important role in polyamine based drug action, i.e. degradation of parent drug
and its metabolites, having significant impact on efficiency of these drugs, and hence for the development of novel N-alkylated polyamine analogues. 相似文献
13.
A homology model of Saccharomyces cerevisiae phosphoenolpyruvate (PEP) carboxykinase (ATP + oxaloacetate ⇄ ADP + PEP + CO2) in complex with its substrates shows that the isobutyl group of Leu460 is in close proximity to the adenine ring of the
nucleotide, while the carboxyl group of Glu299 is within hydrogen-bonding distance of the ribose 2′OH. The Leu460Ala mutation
caused three-fold and seven-fold increases in the K
m for ADPMn− and ATPMn2−, respectively, while the Glu299Ala mutation had no effect. Binding studies showed losses of approximately 2 kcal mol−1 in the nucleotide binding affinity due to the Leu460Ala mutation and no effect for the Glu299Ala mutation. PEP carboxykinase
utilized 2′deoxyADP and 2′deoxyATP as substrates with kinetic and equilibrium dissociation constants very similar to those
of ADP and ATP, respectively. These results show that the hydrophobic interaction between Leu460 and the adenine ring of the
nucleotide significantly contributed to the nucleotide affinity of the enzyme. The 2′deoxy nucleotide studies and the lack
of an effect of the Glu299Ala mutation in nucleotide binding suggest that the possible hydrogen bond contributed by Glu299
and the ribose 2′OH group may not be relevant for nucleotide binding. 相似文献
14.
Eva Corral Anna C. G. Hotze Hans den Dulk Anna Leczkowska Alison Rodger Michael J. Hannon Jan Reedijk 《Journal of biological inorganic chemistry》2009,14(3):439-448
Various interaction modes between a group of six ruthenium polypyridyl complexes and DNA have been studied using a number
of spectroscopic techniques. Five mononuclear species were selected with formula [Ru(tpy)L1L2](2−n)+, and one closely related dinuclear cation of formula [{Ru(apy)(tpy)}2{μ-H2N(CH2)6NH2}]4+. The ligand tpy is 2,2′:6′,2″-terpyridine and the ligand L1 is a bidentate ligand, namely, apy (2,2′-azobispyridine), 2-phenylazopyridine, or 2-phenylpyridinylmethylene amine. The ligand
L2 is a labile monodentate ligand, being Cl−, H2O, or CH3CN. All six species containing a labile L2 were found to be able to coordinate to the DNA model base 9-ethylguanine by 1H NMR and mass spectrometry. The dinuclear cationic species, which has no positions available for coordination to a DNA base,
was studied for comparison purposes. The interactions between a selection of four representative complexes and calf-thymus
DNA were studied by circular and linear dichroism. To explore a possible relation between DNA-binding ability and toxicity,
all compounds were screened for anticancer activity in a variety of cancer cell lines, showing in some cases an activity which
is comparable to that of cisplatin. Comparison of the details of the compound structures, their DNA binding, and their toxicity
allows the exploration of structure–activity relationships that might be used to guide optimization of the activity of agents
of this class of compounds.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
15.
P. O. Vardevanyan A. P. Antonyan G. A. Manukyan A. T. Karapetyan A. K. Shchyolkina O. F. Borisova 《Molecular Biology》2000,34(2):272-276
Isotherms of the EtBr adsorption on native and denatured poly(dA)poly(dT) in the temperature interval 20–70°C were obtained.
The EtBr binding constants and the number of binding sites were determined. The thermodynamic parameters of the EtBr intercalation
complex upon changes of solution temperature 20–48°C were calculated: 1.0·106 M−1≤K≤1.4·106 M−1, free energy ΔG
o=−8.7±0.3 kcal/mol, enthalpy ΔH
o≅0, and entropy ΔS
o=28±0.5 cal/(mol deg). UV melting has shown that the melting temperature (T
m) of EtBr-poly(dA)poly(dT) complexes (μ=0.022,4.16·10−5 M EtBr) increased by 17°C as compared with the ΔT
m of free homopolymer, whereas the half-width of the transition (T
m) is not changed. It was shown for the first time that EtBr forms complexes of two types on single-stranded regions of poly(dA)poly(dT)
denatured at 70°C: strong (K
1=1.7·105 M−1; ΔG
o=−8.10±0.03 kcal/mol) and weak (K
2=2.9·103 M−1; ΔG
o=−6.0±0.3 kcal/mol).The ΔG
o of the strong and weak complexes was independent of the solution ionic strength, 0.0022≤μ≤0.022. A model of EtBr binding
with single-stranded regions of poly(dA)poly(dT) is discussed. 相似文献
16.
Asok Banerjee Sankar N. Maity Sukla Ray Chaudhuri B. Bhattacharyya 《Journal of biosciences》1987,11(1-4):525-536
Colchicine-tubulin dimer comPlex, a Potent inhibitor of normal microtubule assembly undergoes extensive self-assembly in the
Presence of 1 X 10-4 M zinc sulPhate. Polymers assembled from colchicine-tubulin dimer comPlexes are sensitive to cold.
Although colchicine can be accomodated within the Polymeric structure, the drug cannot bind to tubulin subunits in the intact
Polymers. This is evidenced by the fact that (a) the colchicine binding activity of tubulin is lost when allowed to Polymerize
with zinc sulPhate, (b) the loss in colchicine binding could be Prevented by Preincubation of tubulin with 1 X 10-3 M CaCl2 or 1 X 10-5 M vinblastine sulPhate and finally (c) no loss in colchicine binding activity is found when tubulin is kePt at a concentration
far below the critical concentration for Polymerization. Unlike colchicine, its B-ring analogues desacetamido colchicine (devoid
of the B-ring subtituent) and 2-methoxy-5-(2′, 3′, 4′-trimethoxyPhenyl) troPone (devoid of the B-ring) can bind to tubulin
subunits in the intact Polymers.
Thus we conclude that the colchicine binding domain on the tubulin molecule is mostly (if not comPletely) exPosed in the Zn(II)
-induced Polymers and the B-ring substituent Plays a major role in determining the binding ability of a colchicine analogue
to tubulin in the intact Zn(II) -induced sheets. 相似文献
17.
Jayati Roy Choudhury Lu Rao Ulrich Bierbach 《Journal of biological inorganic chemistry》2011,16(3):373-380
A restriction enzyme cleavage inhibition assay was designed to determine the rates of DNA platination by four non-cross-linking
platinum–acridine agents represented by the formula [Pt(am2)LCl](NO3)2, where am is a diamine nonleaving group and L is an acridine derived from the intercalator 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea
(ACRAMTU). The formation of monofunctional adducts in the target sequence 5′-CGA was studied in a 40-base-pair probe containing
the EcoRI restriction site GAATTC. The time dependence of endonuclease inhibition was quantitatively analyzed by polyacrylamide gel
electrophoresis. The formation of monoadducts is approximately 3 times faster with double-stranded DNA than with simple nucleic
acid fragments. Compound 1 (am2 is ethane-1,2-diamine, L is ACRAMTU) reacts with a first-order rate constant of k
obs = 1.4 ± 0.37 × 10−4 s−1 (t
1/2 = 83 ± 22 min). Replacement of the thiourea group in ACRAMTU with an amidine group (compound 2) accelerates the rate by fourfold (k
obs = 5.7 ± 0.58 × 10−4 s−1, t
1/2 = 21 ± 2 min), and introduction of a propane-1,3-diamine nonleaving group results in a 1.5-fold enhancement in reactivity
(compound 3, k
obs = 2.1 ± 0.40 × 10−4 s−1, t
1/2 = 55 ± 10 min) compared with the prototype. Derivative 4, containing a 4,9-disubstituted acridine threading intercalator, was the least reactive compound in the series (k
obs = 1.1 ± 0.40 × 10−4 s−1, t
1/2 = 104 ± 38 min). The data suggest a correlation may exist between the binding rates and the biological activity of the compounds.
Potential pharmacological advantages of rapid formation of cytotoxic monofunctional adducts over the common purine–purine
cross-links are discussed. 相似文献
18.
Isatin-3-isonicotinylhydrazone was synthesized and characterized. The interaction of native calf thymus DNA with isatin-3-isonicotinylhydrazone
(IINH) in 10 mM Tris–HCl aqueous solutions at neutral pH 7.4 has been investigated by spectrophotometric, circular dichroism
(CD), melting temperature (T
m
), spectrofluorimetric, and viscometric techniques. It is found that IINH molecules could intercalate between base pairs of
DNA as are evidenced by: hypochromism in UV absorption band of IINH, induced CD spectral changes, sharp increase in specific
viscosity of DNA, and increase in the fluorescence of methylene blue (MB)-DNA solutions in the presence of increasing amounts
of IINH, which indicates that it is able to release the intercalated MB completely. The binding constants of IINH–DNA complex
at four different temperatures (277, 288, 298, and 310 K) were calculated to be 4.7 × 104, 2.2 × 104, 1.75 × 104 and 1.1 × 104 M−1, respectively. Furthermore, the enthalpy and entropy of the reaction between IINH and CT-DNA showed that the reaction is
enthalpy-favored and entropy- disfavored (∆H = −30.187 kJ mol−1; ∆S = −20.46 J mol−1K−1) which are other evidences to indicate the IINH is able to be intercalated in the DNA base pairs. 相似文献
19.
Paolo Ascenzi Alessandro Bolli Alessandra di Masi Grazia R. Tundo Gabriella Fanali Massimo Coletta Mauro Fasano 《Journal of biological inorganic chemistry》2011,16(1):97-108
Human serum heme–albumin (HSA-heme) displays globin-like properties. Here, the allosteric inhibition of ferric heme [heme-Fe(III)]
binding to human serum albumin (HSA) and of ferric HSA–heme [HSA-heme-Fe(III)]-mediated peroxynitrite isomerization by isoniazid
and rifampicin is reported. Moreover, the allosteric inhibition of isoniazid and rifampicin binding to HSA by heme-Fe(III)
has been investigated. Data were obtained at pH 7.2 and 20.0 °C. The affinity of isoniazid and rifampicin for HSA [K
0 = (3.9 ± 0.4) × 10−4 and (1.3 ± 0.1) × 10−5 M, respectively] decreases by about 1 order of magnitude upon heme-Fe(III) binding to HSA [K
h = (4.3 ± 0.4) × 10−3 and (1.2 ± 0.1) × 10−4 M, respectively]. As expected, the heme-Fe(III) affinity for HSA [H
0 = (1.9 ± 0.2) × 10−8 M] decreases by about 1 order of magnitude in the presence of saturating amounts of isoniazid and rifampicin [H
d = (2.1 ± 0.2) × 10−7 M]. In the absence and presence of CO2, the values of the second-order rate constant (l
on) for peroxynitrite isomerization by HSA-heme-Fe(III) are 4.1 × 105 and 4.3 × 105 M−1 s−1, respectively. Moreover, isoniazid and rifampicin inhibit dose-dependently peroxynitrite isomerization by HSA-heme-Fe(III)
in the absence and presence of CO2. Accordingly, isoniazid and rifampicin impair in a dose-dependent fashion the HSA-heme-Fe(III)-based protection of free l-tyrosine against peroxynitrite-mediated nitration. This behavior has been ascribed to the pivotal role of Tyr150, a residue
that either provides a polar environment in Sudlow’s site I (i.e., the binding pocket of isoniazid and rifampicin) or protrudes
into the heme-Fe(III) cleft, depending on ligand binding to Sudlow’s site I or to the FA1 pocket, respectively. These results
highlight the role of drugs in modulating heme-Fe(III) binding to HSA and HSA-heme-Fe(III) reactivity. 相似文献
20.
Identification of QTL underlying isoflavone contents in soybean seeds among multiple environments 总被引:3,自引:0,他引:3
Guoliang Zeng Dongmei Li Yingpeng Han Weili Teng Jian Wang Liquan Qiu Wenbin Li 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2009,118(8):1455-1463
Soybean isoflavones are valued in certain medicines, cosmetics, foods and feeds. Selection for high-isoflavone content in
seeds along with agronomic traits is a goal of many soybean breeders. The aim of the study was to identify the quantitative
trait loci (QTL) underlying seed isoflavone content in soybean among seven environments in China. A cross was made between
‘Zhongdou 27’, a soybean cultivar with higher mean isoflavone content in the seven environments (daidzein, DZ, 1,865 μg g−1; genistein, GT, 1,614 μg g−1; glycitein, GC, 311 μg g−1 and total isoflavone, TI, 3,791 μg g−1) and ‘Jiunong 20’, a soybean cultivar with lower isoflavone content (DZ, 844 μg g−1; GT, 1,046 μg g−1; GC, 193 μg g−1 and TI, 2,061 μg g−1). Through single-seed-descent, 130 F5-derived F6 recombinant inbred lines were advanced. A total of 99 simple-sequence repeat markers were used to construct a genetic linkage
map. Seed isoflavone contents were analyzed using high-performance liquid chromatography for multiple years and locations
(Harbin in 2005, 2006 and 2007, Hulan in 2006 and 2007, and Suihua in 2006 and 2007). Three QTL were associated with DZ content,
four with GT content, three with GC content, and five with TI content. For all QTL detected the beneficial allele was from
Zhongdou 27. QTL were located on three (DZ), three (GC), four (GT) and five (TI) molecular linkage groups (LG). A novel QTL
was detected with marker Satt144 on LG F that was associated with DZ (0.0014 > P > 0.0001, 5% < R
2 < 11%; 254 < DZ < 552 μg g−1), GT (0.0027 > P > 0.0001; 4% < R
2 < 9%; 262 < GT < 391 μg g−1), and TI (0.0011 > P > 0.0001; 4% < R
2 < 15%; 195 < TI < 871 μg g−1) across the various environments. A previously reported QTL on LG M detected by Satt540 was associated with TI across four
environments and TI mean (0.0022 > P > 0.0001; 3% < R
2 < 8%; 182 < TI < 334 μg g−1) in China. Because both beneficial alleles were from Zhongdou 27, it was concluded that these two QTL would have the greatest
potential value for marker-assisted selection for high-isoflavone content in soybean seed in China.
G. Zeng, D. Li and Y. Han have equal contributions to the paper. 相似文献