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DNA Cleavage (dna + cleavage)
Terms modified by DNA Cleavage Selected AbstractsTunable DNA Cleavage by Intercalating PeptidoconjugatesCHEMBIOCHEM, Issue 5 2006Kerry P. Mahon Jr. Abstract The properties of a novel family of peptide-based DNA-cleavage agents are described. Examination of the DNA-cleavage activities of a systematic series of peptide,intercalator conjugates revealed trends that show a strong dependence on peptide sequence. Conjugates differing by a single residue displayed reactivities that varied over a wide range. The cleavage activity was modulated by the electrostatic or steric qualities of individual amino acids. Isomeric conjugates that differed in the position of the tether also exhibited different reactivities. The mechanism of DNA cleavage for these compounds was also probed and was determined to involve hydrogen-atom abstraction from the DNA backbone. Previous studies of these compounds indicated that amino acid peroxides were the active agents in the cleavage reaction; in this report, the chemistry underlying the reaction is characterized. The results reported provide insight into how peptide sequences can be manipulated to produce biomimetic compounds. [source] Optimization of Triple-Helix-Directed DNA Cleavage by Benzoquinoquinoxaline,Ethylenediaminetetraacetic Acid ConjugatesCHEMBIOCHEM, Issue 9 2003Rula Zain Dr. Abstract The formation of triple-helical structures of DNA is based on sequence-specific recognition of oligopyrimidine,oligopurine stretches of double-helical DNA. Triple-helical structures can be stabilized by DNA-binding ligands. Benzoquinoquinoxaline (BQQ) derivatives are among the most potent intercalating-type agents known to stabilize DNA triple-helical structures. We previously reported the conversion of BQQ into a triplex-directed DNA cleaving agent, namely BQQ,ethylenediaminetetraacetic acid (EDTA), by coupling of 6-(3-aminopropylamino)BQQ to a suitable ethylenediaminetetraacetic acid derivative, and we demonstrated the ability of this conjugate to cause double-stranded cleavage of DNA at the triplex site. However, this prototype derivative BQQ,EDTA conjugate showed lower affinity towards triplex DNA than BQQ itself. In the light of this observation, and guided by molecular modeling studies, we synthesized a second generation of BQQ,EDTA conjugates based on 6-[bis(2-aminoethyl)amino]- and 6-(3,3,-diamino- N -methyldipropylamino),BQQ derivatives. We confirmed by DNA melting experiments that the new conjugates displayed an increased specific affinity towards triple helices when compared to the previously synthesized BQQ,EDTA. In addition, the efficiency of these new agents in triplex-specific binding and cleavage was demonstrated by triplex-directed double-stranded cleavage of plasmid DNA. [source] ChemInform Abstract: N-Propargyl-2-alkynylbenzothiazolium Aza-enediynes: Role of the 2-Alkynylbenzothiazolium Functionality in DNA Cleavage.CHEMINFORM, Issue 9 2002Dalip Kumar Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Unique Ligand-Based Oxidative DNA Cleavage by Zinc(II) Complexes of Hpyramol and HpyrimolCHEMISTRY - A EUROPEAN JOURNAL, Issue 18 2007Palanisamy, Uma Maheswari Dr. Abstract The zinc(II) complexes reported here have been synthesised from the ligand 4-methyl-2- N -(2-pyridylmethyl)aminophenol (Hpyramol) with chloride or acetate counterions. All the five complexes have been structurally characterised, and the crystal structures reveal that the ligand Hpyramol gradually undergoes an oxidative dehydrogenation to form the ligand 4-methyl-2- N -(2-pyridylmethylene)aminophenol (Hpyrimol), upon coordination to ZnII. All the five complexes cleave the ,X174 phage DNA oxidatively and the complexes with fully dehydrogenated pyrimol ligands were found to be more efficient than the complexes with non-dehydrogenated Hpyramol ligands. The DNA cleavage is suggested to be ligand-based, whereas the pure ligands alone do not cleave DNA. The DNA cleavage is strongly suggested to be oxidative, possibly due to the involvement of a non-diffusible phenoxyl radical mechanism. The enzymatic religation experiments and DNA cleavage in the presence of different radical scavengers further support the oxidative DNA cleavage by the zinc(II) complexes. [source] Efficient DNA Cleavage Induced by Copper(II) Complexes of Hydrolysis Derivatives of 2,4,6-Tri(2-pyridyl)-1,3,5-triazine in the Presence of Reducing AgentsEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 6 2007Joaquín Borrás Abstract The reaction of 2,4,6-tri(pyridyl)-1,3,5-triazine (ptz) and copper(II) salts in dmf/water (1:1) results in the hydrolysis of ptz and formation of the anions bis(2-pyridylcarbonyl)amide (ptO2,) and bis(2-pyridylamine)amide (ptN2,), which are found in the complexes [Cu(ptN2)(OAc)]·3H2O (1), [Cu(ptO2)(OAc)(H2O)]·H2O (2), [Cu(ptN2)(for)]·3H2O (3) (for = formate), [Cu(ptO2)(for)(H2O)] (4), [Cu(ptO2)(benz)]·H2O (5) (benz = benzoate), and [Cu(ptO2)F(H2O)]2·3H2O (6). This report includes the chemical and spectroscopic characterization of all these complexes along with the crystal structures of 4,6. The coordination spheres of CuII in 4 and 5 are best described as distorted tetragonal square pyramidal for the former and distorted square planar for the latter. The crystal structure of 6 shows the presence of two discrete monomeric [Cu(ptO2)F(H2O)] entities in the crystallographic asymmetric unit in which both copper(II) ions have a distorted square-pyramidal coordination geometry. The binding of the complexes to DNA has been investigated with the aid of viscosity and thermal denaturation studies, both of which indicate that the interaction is probably due to the outer-sphere mechanism. The ability of the compounds to cleave DNA has also been tested. Efficient oxidative cleavage was observed in the presence of a mild reducing agent (ascorbate) and dioxygen. Mechanistic studies with reactive oxygen species (ROS) scavengers confirm that hydrogen peroxide, the hydroxyl radical, singlet oxygen-like species, and the superoxide anion are necessary diffusible intermediates in the scission process. A mechanism involving either the Fenton or theHaber,Weiss reaction plus the formation of copper oxene species is proposed for the DNA cleavage mediated by these compounds.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] An allosteric DNAzyme with dual RNA-cleaving and DNA-cleaving activitiesFEBS JOURNAL, Issue 11 2010Dazhi Jiang A series of RNA-cleaving or DNA-cleaving DNAzymes have been obtained by in vitro selection. However, engineering an allosteric DNAzyme with dual RNA-cleaving and DNA-cleaving activities is very challenging. We used an in vitro -selected pistol-like (PL) DNAzyme as a DNA scaffold for designing a DNAzyme with dual catalytic activities. We prepared the 46-nucleotide DNAzyme with DNA-cleaving activity (PL DNAzyme), and then grafted the deoxyribonucleotide residues from an 8,17 variant DNAzyme into the region of stem,loop I and the catalytic core of the PL DNAzyme scaffold. This deoxyribonucleotide residue grafting resulted in a DNAzyme with dual RNA-cleaving and DNA-cleaving activities (DRc DNAzyme). Drc DNAzyme has properties different from those of the original PL DNAzyme, including DNA cleavage sites and the required metal ion concentration. Interestingly, the RNA substrate and RNase A can act as effectors to mediate the DNA cleavage. Our results show that RNA-cleaving and DNA-cleaving activities simultaneously coexist in DRc DNAzyme, and the DNA cleavage activity can be reversibly regulated by a conformational transition. [source] Internucleosomal DNA cleavage in apoptotic WEHI 231 cells is mediated by a chymotrypsin-like proteaseGENES TO CELLS, Issue 11 2004Jernej Murn Although several lines of evidence support a role for serine proteases in apoptosis, little is known about the mechanisms involved. In the present study, we have examined the apoptosis-inducing potential and dissected the death-signalling pathways of N-tosyl-L-phenylalanine chloromethyl ketone (TPCK) and N-tosyl-L-lysine chloromethyl ketone (TLCK), inhibitors of chymotrypsin- and trypsin-like proteases, respectively. Our results designate two distinct roles for serine proteases. Firstly, we show that both inhibitors induce biochemical and morphological characteristics of apoptosis, including proteolysis of poly(ADP-ribose) polymerase 1 (PARP-1) and inhibitor of caspase-activated DNase (ICAD), as well as mitochondrial dysfunction, and that their action is abrogated by the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp.fluoromethylketone (z-VAD.fmk). These results suggest that inhibition of anti-apoptotic serine proteases governs the onset of the caspase-dependant apoptotic cascade. Secondly, we also demonstrate the involvement of a serine protease in the terminal stage of apoptosis. We showed that chymotrypsin-like protease activity is required for internucleosomal DNA fragmentation in apoptotic cells. Hence, DNA fragmentation is abrogated in TPCK-pre-treated WEHI 231 cells undergoing apoptosis triggered either by anti-IgM or TLCK. These results indicate that internucleosomal DNA cleavage in apoptotic cells is mediated by a chymotrypsin-like protease. [source] VDE-initiated intein homing in Saccharomyces cerevisiae proceeds in a meiotic recombination-like mannerGENES TO CELLS, Issue 7 2003Tomoyuki Fukuda Background: Inteins and group I introns found in prokaryotic and eukaryotic organisms occasionally behave as mobile genetic elements. During meiosis of the yeast Saccharomyces cerevisiae, the site-specific endonuclease encoded by VMA1 intein, VDE, triggers a single double-strand break (DSB) at an inteinless allele, leading to VMA1 intein homing. Besides the accumulating information on the in vitro activity of VDE, very little has been known about the molecular mechanism of intein homing in yeast nucleus. Results: We developed an assay to detect the product of VMA1 intein homing in yeast genome. We analysed mutant phenotypes of RecA homologs, Rad51p and Dmc1p, and their interacting proteins, Rad54p and Tid1p, and found that they all play critical roles in intein inheritance. The absence of DSB end processing proteins, Sae2p and those in the Mre11-Rad50-Xrs2 complex, also causes partial reduction in homing efficiency. As with meiotic recombination, crossover events are frequently observed during intein homing. We also observed that the absence of premeiotic DNA replication caused by hydroxyurea (HU) or clb5, clb6, mutation reduces VDE-mediated DSBs. Conclusion: The repairing system working in intein homing shares molecular machinery with meiotic recombination induced by Spo11p. Moreover, like Spo11p-induced DNA cleavage, premeiotic DNA replication is a prerequisite for a VDE-induced DSB. VMA1 intein thus utilizes several host factors involved in meiotic and recombinational processes to spread its genetic information and guarantee its progeny through establishment of a parasitic relationship with the organism. [source] Non-apoptogenic killing of hela cervical carcinoma cells after short exposure to the alkylating agent N -methyl- N, -nitro- N -nitrosoguanidine (MNNG)JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2003Józefa W, sierska-G Abstract We examined the action of N -methyl- N, -nitro- N -nitrosoguanidine (MNNG) on HeLa cells and compared it with that of cisplatin (CP). MNNG directly killed a substantial number of cells within 1 hour and resulted in strong DNA-damage as evidenced by Comet measurements. Despite appearance of DNA lesions, p53 protein was not activated. Analysis of HeLa cells treated with MNNG for 1h, 3h and 6h by flow cytometry and by Hoechst staining did not reveal any sub-G1 cell population and chromatin condensation/fragmentation characteristic for apoptosis, respectively. Also, no biochemical changes typical for apoptosis such as activation of caspase-3 or release of cytochrome C from mitochondria were detected. Inactivation of PARP-1 reduced the direct cytotoxicity exerted by MNNG. Our results showing that despite appearance of severe DNA lesions after short exposure of HeLa cells to MNNG neither activation of p53 response nor induction of apoptosis occurred implicate that generation of strong DNA damage is not sufficient to stabilize p53 protein in HeLa cells. Our data unequivocally show that the conscientious determination of the type of cell death induced by genotoxic agents is necessary. The assessment of the changes based on at least a few independent criteria is required to discriminate between apoptosis and necrosis. Since the alkylating agents generate DNA strand breaks, the recruitment of methods based on determination of DNA cleavage such as DNA ladder or TUNEL assay for evaluation of apoptosis is not adequate. © 2003 Wiley-Liss, Inc. [source] Theoretical study of the interaction between a high-valent manganese porphyrin oxyl-(hydroxo)-Mn(IV)-TMPyP and double-stranded DNAJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 7 2003Philippe Arnaud Abstract Cationic porphyrin derivatives such as meso-tetrakis(4- N -methylpyridinium)porphyrin, TMPyP, have been shown to interact with double-stranded DNA. The manganese derivative, Mn(III)-TMPyP, activated by an oxygen donor like potassium monopersulfate, provides an efficient DNA-cleaving system. Previous experimental work1 has shown that DNA cleavage by the Mn(III)-TMPyP/KHSO5 system was due to an oxidative attack, within the minor groove of B-DNA, at the C5, or C1, carbons of deoxyribose units. The aim of this study was to use molecular modeling to elucidate the specificity of the interactions between the transient active species oxyl-Mn(IV)-TMPyP and the DNA target. Geometric parameters, charges, and force field constants consistent with the AMBER 98 force field were calculated by DFT methods. Molecular modeling (mechanics and dynamic simulations) were performed for oxyl-(hydroxo)-Mn(IV)-TMPyP bound in the minor groove of the dodecamer d(5,-TCGTCAAACCGC)-d(5,-GCGGTTTGACGA). Geometry, interactions, and binding energy of the metalloporphyrin located at the A.T triplet region of the dodecamer were analyzed. These studies show no significant structural change of the DNA structure upon ligand binding. Mobility of the metalloporphyrin in the minor groove was restrained by the formation of a hydrogen bond between the hydroxo ligand trans to the metal-oxyl and a DNA phosphate, restricting the access of the oxyl group to the (pro-S) H atom at C5,. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 797,805, 2003 [source] ANTHOCYANIN INTERACTIONS WITH DNA: INTERCALATION, TOPOISOMERASE I INHIBITION AND OXIDATIVE REACTIONSJOURNAL OF FOOD BIOCHEMISTRY, Issue 5 2008MICHAEL R. WEBB ABSTRACT Anthocyanins and their aglycone anthocyanidins are pigmented flavonoids found in significant amounts in many commonly consumed foods. They exhibit a complex chemistry in aqueous solution, which makes it difficult to study their chemistry under physiologic conditions. Here we used a gel electrophoresis assay employing supercoiled DNA plasmid to examine the ability of these compounds (1) to intercalate DNA; (2) to inhibit human topoisomerase I through both inhibition of plasmid relaxation activity (catalytic inhibition) and stabilization of the cleavable DNA,topoisomerase complex (poisoning); and (3) to inhibit or enhance oxidative single-strand DNA nicking. We found no evidence of DNA intercalation by anthocyan(id)ins in the physiologic pH range for any of the compounds used in this study , cyanidin chloride, cyanidin 3- O -glucoside, cyanidin 3,5- O -diglucoside, malvidin 3- O -glucoside and luteolinidin chloride. The anthocyanins inhibited topoisomerase relaxation activity only at high concentrations (>50 µM), and we could find no evidence of topoisomerase I cleavable complex stabilization by these compounds. However, we observed that all of the anthocyan(id)ins used in this study were capable of inducing significant oxidative DNA strand cleavage (nicking) in the presence of 1 mM dithiothreitol, while the free radical scavenger, dimethyl sulfoxide (DMSO), at concentrations typically used in similar studies, completely inhibited DNA nicking. Finally, we proposed a mechanism to explain the anthocyan(id)in-induced oxidative DNA cleavage observed under our experimental conditions. PRACTICAL APPLICATIONS This study provided improved understanding of the mechanisms by which anthocyan(id)ins interact with DNA. By characterizing the chemistry and solution properties of these important dietary components, we obtained improved information on how the anthocyan(id)ins might function in living systems. [source] Cell death and apoptosis-related proteins in muscle biopsies of sporadic amyotrophic lateral sclerosis and polyneuropathyMUSCLE AND NERVE, Issue 8 2001Benedikt G.H. Schoser MD Abstract To investigate disease-related differences of cell death and apoptosis in human denervation atrophy, we studied DNA fragmentation by the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) method in 38 biopsies of clinically nonaffected and affected muscles from patients with sporadic amyotrophic lateral sclerosis (sALS), in 13 muscle biopsies from patients with chronic peripheral neuropathies, and in 8 biopsies from control subjects. In addition, expression of apoptosis-related proteins, bax, bcl-2, and Fas, was studied in 20 biopsies of sALS and 10 chronic peripheral neuropathies. We identified DNA cleavage in 10% of myofibers of patients and in up to 1.5% of control samples. In clinically affected muscles of ALS, a larger amount of TUNEL-positive myofibers (mean 10.5 ± 5.9%) was detected, similar to chronic peripheral neuropathies (mean 10.0 ± 7.4%). Atrophic myofibers were immunopositive for bax, bcl-2, and, to a weaker extent, for Fas. However, bax-, bcl-2-, or Fas-positive atrophic myofibers did not reveal consecutive DNA cleavage. Differences between sALS subgroups and chronic peripheral neuropathies were not found. In human denervation atrophy the bcl-2/bax and the FasL/Fas systems are apparently active independently of DNA fragmentation and apoptosis. DNA fragmentation thus displays an additional reaction that is not disease-specific at chronic stages of human denervation processes, probably recapitulating events like skeletal muscle fiber remodeling in embryonic skeletal tissue development. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 1083,1089, 2001 [source] Free radical scavenging capacity and protective effect of Bacopa monniera L. on DNA damagePHYTOTHERAPY RESEARCH, Issue 8 2003Alessandra Russo Abstract Bacopa monniera L. (family Scrophulariaceae) (BM) is an Ayurvedic medicine, clinically used for memory enhancing, epilepsy, insomnia and as a mild sedative. In this work, the free radical scavenging capacity of a methanol extract of BM and the effect on DNA cleavage induced by H2O2 UV-photolysis was investigated. In addition, we examined whether this plant extract is capable of reducing the hydrogen peroxide-induced cytotoxicity and DNA damage in human non-immortalized ,broblasts. It showed a dose-dependent free radical scavenging capacity and a protective effect on DNA cleavage. These results were con,rmed by a signi,cant protective effect on H2O2 , induced cytoxicity and DNA damage in human non-immortalized ,broblasts. The antioxidant capacity of BM may explain, at least in part, the reported antistress, immunomodulatory, cognition-facilitating, antiin,ammatory and antiaging effects produced by it in experimental animals and in clinical situations and may justify further investigation of its other bene,cial properties. Moreover, this experimental evidence suggests that because of its antioxidant activity, this Ayurvedic drug may be useful in the treatment of human pathologies in which free radical production plays a key role. Copyright © 2003 John Wiley & Sons, Ltd. [source] Synthesis, structure and DNA cleavage of mononuclear Fe(III) complexes with 1,2,4-triazole-base ligandAPPLIED ORGANOMETALLIC CHEMISTRY, Issue 9 2010Hui Liu Abstract Two new mononuclear iron(III) complexes, [Fe(HL)2](ClO4) · (H2O)1.75· CH3CN (1) and [Fe(HL)Cl2] · DMF (2) [H2L = 3-(2-phenol)-5-(pyridin-2-yl)-1,2,4-triazole] have been synthesized and characterized by X-ray single-crystal structure analysis. The single crystal X-ray crystallographic studies reveal that the central iron atom has a distorted octahedral environment for 1 and a distorted square pyramidal geometry for 2. The DNA cleavage activity of the iron(III) complexes was measured, indicating that the six-coordinated iron(III) (complex 1) was cleavage inactive and only five-coordinated complex 2 effectively promoted the cleavage of plasmid DNA in the presence and/or absence of activating agents (peroxide oxygen) at physiological pH and temperature. The mechanism of plasmid DNA cleavage was also studied by adding standard radical scavengers. Copyright © 2010 John Wiley & Sons, Ltd. [source] Ferrocene-bridging dinuclear cyclen copper(II) complexes as high efficient artificial nucleases: design, synthesis and interaction with DNAAPPLIED ORGANOMETALLIC CHEMISTRY, Issue 5 2008Kun Li Abstract Two novel cyclen copper(II) complexes bridged by ferrocene were designed and synthesized. Both of these complexes exhibited excellent cleavage ability towards plasmid DNA via an oxidative pathway without the presence of any additives. Cyclic voltammetry was used to investigate the electrochemistry characters of the interaction between the complexes and DNA. Agarose gel electrophoresis was carried out to study the DNA restriction ability of these complexes, and the results indicated that the complexes showed higher cleavage efficiency via an oxidative pathway without the presence of any additives. The mechanism of DNA cleavage catalyzed by these complexes was examined by the addition of various scavengers, and the results showed that singlet oxygen and hydroxyl radical might be responsible for the cleavage process. Copyright © 2008 John Wiley & Sons, Ltd. [source] A novel carbazole topoisomerase II poison, ER-37328: potent tumoricidal activity against human solid tumors in vitro and in vivoCANCER SCIENCE, Issue 1 2003Katsuji Nakamura We have discovered a novel topoisomerase II (topo II) poison, ER-37328 (12,13-dihydro-5-[2-(dimethylamino)ethyl]-4H-benzo[c]py-rimido[5,6,1- jk]carbazole-4,6,10(5H, 11H)-trione hydrochloride), which shows potent tumor regression activity against Colon 38 cancer inoculated s.c. Here, we describe studies on the cell-killing activity against a panel of human cancer cell lines and the antitumor activity of ER-37328 against human tumor xenografts. In a cell-killing assay involving 1-h drug treatment, ER-37328 showed more potent cell-killing activity (50% lethal concentrations (LC50s) ranging from 2.9 to 20 ,M) than etoposide (LC50s>60 ,M) against a panel of human cancer cell lines. ER-37328 induced double-stranded DNA cleavage, an indicator of topo II-DNA cleavable complex formation, within 1 h in MX-1 cells, and the extent of cleavage showed a bell-shaped relationship to drug concentration, with the maximum at 2.5 ,M. After removal of the drug (2.5 ,M) at 1 h, incubation was continued in drug-free medium, and the amount of cleaved DNA decreased. However, at 10 ,M, which is close to the LC50 against MX-1 cells, DNA cleavage was not detected immediately after 1-h treatment, but appeared and increased after drug removal. This result may explain the potent cell-killing activity of ER37328 in the 1-h treatment. In vivo, ER-37328 showed potent tumor regression activity against MX-1 and NS-3 tumors. Moreover, ER-37328 had a different antitumor spectrum from irinotecan or cisplatin against human tumor xenografts. In conclusion, ER-37328 is a promising topo II poison with strong cell killing activity in vitro and tumor regression activity in vivo, and is a candidate for the clinical treatment of malignant solid tumors. (Cancer Sci 2003; 94: 119,124) [source] Peptidoglycan induces loss of a nuclear peptidoglycan recognition protein during host tissue development in a beneficial animal-bacterial symbiosisCELLULAR MICROBIOLOGY, Issue 7 2009Joshua V. Troll Summary Peptidoglycan recognition proteins (PGRPs) are mediators of innate immunity and recently have been implicated in developmental regulation. To explore the interplay between these two roles, we characterized a PGRP in the host squid Euprymna scolopes (EsPGRP1) during colonization by the mutualistic bacterium Vibrio fischeri. Previous research on the squid-vibrio symbiosis had shown that, upon colonization of deep epithelium-lined crypts of the host light organ, symbiont-derived peptidoglycan monomers induce apoptosis-mediated regression of remote epithelial fields involved in the inoculation process. In this study, immunofluorescence microscopy revealed that EsPGRP1 localizes to the nuclei of epithelial cells, and symbiont colonization induces the loss of EsPGRP1 from apoptotic nuclei. The loss of nuclear EsPGRP1 occurred prior to DNA cleavage and breakdown of the nuclear membrane, but followed chromatin condensation, suggesting that it occurs during late-stage apoptosis. Experiments with purified peptidoglycan monomers and with V. fischeri mutants defective in peptidoglycan-monomer release provided evidence that these molecules trigger nuclear loss of EsPGRP1 and apoptosis. The demonstration of a nuclear PGRP is unprecedented, and the dynamics of EsPGRP1 during apoptosis provide a striking example of a connection between microbial recognition and developmental responses in the establishment of symbiosis. [source] Tunable DNA Cleavage by Intercalating PeptidoconjugatesCHEMBIOCHEM, Issue 5 2006Kerry P. Mahon Jr. Abstract The properties of a novel family of peptide-based DNA-cleavage agents are described. Examination of the DNA-cleavage activities of a systematic series of peptide,intercalator conjugates revealed trends that show a strong dependence on peptide sequence. Conjugates differing by a single residue displayed reactivities that varied over a wide range. The cleavage activity was modulated by the electrostatic or steric qualities of individual amino acids. Isomeric conjugates that differed in the position of the tether also exhibited different reactivities. The mechanism of DNA cleavage for these compounds was also probed and was determined to involve hydrogen-atom abstraction from the DNA backbone. Previous studies of these compounds indicated that amino acid peroxides were the active agents in the cleavage reaction; in this report, the chemistry underlying the reaction is characterized. The results reported provide insight into how peptide sequences can be manipulated to produce biomimetic compounds. [source] Synthesis, DNA-Binding, Cleavage, and Cytotoxic Activity of New 1,7-Dioxa-4,10-diazacyclododecane Artificial Receptors Containing Bisguanidinoethyl or Diaminoethyl Double Side ArmsCHEMISTRY - A EUROPEAN JOURNAL, Issue 34 2007Xin Sheng Abstract Novel 1,7-dioxa-4,10-diazacyclododecane artificial receptors with two pendant aminoethyl (3) or guanidinoethyl (4) side arms have been synthesized. Spectroscopy, including fluorescence and CD spectroscopy, of the interactions of 3, 4, and their copper(II) complexes with calf thymus DNA indicated that the DNA binding affinity of these compounds follows the order Cu2+,4>Cu2+,3>4>3, and the binding constants of Cu2+,3 are Cu2+,4 are 7.2×104 and 8.7×104,M,1, respectively. Assessment by agarose gel electrophoresis of the plasmid pUC,19 DNA cleavage activity in the presence of the receptors showed that the complexes Cu2+,3 and Cu2+,4 exhibit powerful supercoiled DNA cleavage efficiency. Kinetic data of DNA cleavage promoted by Cu2+,3 and Cu2+,4 under physiological conditions fit to a saturation kinetic profile with kmax values of 0.865 and 0.596,h,1, respectively, which give about 108 -fold rate acceleration over uncatalyzed supercoiled DNA. This acceleration is due to efficient cooperative catalysis of the copper(II) center and the functional (diamino or bisguanidinium) groups. In-vitro cytotoxic activities toward murine melanoma B16 cells and human leukemia HL-60 cells were also examined: Cu2+,4 shows the highest activity with IC50 values of 1.62×10,4 and 1.19×10,5,M, respectively. [source] Unique Ligand-Based Oxidative DNA Cleavage by Zinc(II) Complexes of Hpyramol and HpyrimolCHEMISTRY - A EUROPEAN JOURNAL, Issue 18 2007Palanisamy, Uma Maheswari Dr. Abstract The zinc(II) complexes reported here have been synthesised from the ligand 4-methyl-2- N -(2-pyridylmethyl)aminophenol (Hpyramol) with chloride or acetate counterions. All the five complexes have been structurally characterised, and the crystal structures reveal that the ligand Hpyramol gradually undergoes an oxidative dehydrogenation to form the ligand 4-methyl-2- N -(2-pyridylmethylene)aminophenol (Hpyrimol), upon coordination to ZnII. All the five complexes cleave the ,X174 phage DNA oxidatively and the complexes with fully dehydrogenated pyrimol ligands were found to be more efficient than the complexes with non-dehydrogenated Hpyramol ligands. The DNA cleavage is suggested to be ligand-based, whereas the pure ligands alone do not cleave DNA. The DNA cleavage is strongly suggested to be oxidative, possibly due to the involvement of a non-diffusible phenoxyl radical mechanism. The enzymatic religation experiments and DNA cleavage in the presence of different radical scavengers further support the oxidative DNA cleavage by the zinc(II) complexes. [source] DNA Topoisomerase I Inhibitory Alkaloids from Corydalis saxicolaCHEMISTRY & BIODIVERSITY, Issue 7 2008Xuanxuan Cheng Abstract Chemical studies of the Chinese herb Corydalis saxicolaBunting led to the isolation and identification of 14 alkaloids, 1,14. Seven of these compounds, 4,9 and 11, were obtained from this plant for the first time. Feruloylagmatine (7) is the first guanidine-type alkaloid to be identified in the family Papaveraceae and in dicotyledonous plants. All of the isolated compounds were assayed for inhibitory activity against human DNA topoisomerase I. A DNA cleavage assay demonstrated that these alkaloids specifically inhibit topoisomerase through stabilization of the enzyme,DNA complex. Among the isolated alkaloids, (,)-pallidine (8) and (,)-scoulerine (11) showed strong inhibitory activities toward topoisomerase I that were comparable to camptothecin, a typical topoisomerase I inhibitor. A preliminary structure,activity relationship study suggested that the quaternary ammonium ion might play an important role in topoisomerase I inhibition by the isoquinoline alkaloids. These data indicated that DNA topoisomerase I inhibition represents probably one of the anticarcinogenic mechanisms of C. saxicola. [source] Impact of the Aliphatic Dicarboxylate Chain of Novel Dinuclear Palladium(II) Complexes: Synthesis and Biological EvaluationCHINESE JOURNAL OF CHEMISTRY, Issue 2 2010Enjun Gao Abstract Five dinuclear palladium(II) complexes with HOOC(CH2)nCOOH (n=2,6) and 2,2,-bipyridine ligands were synthesigned by a reaction with K2PdCl4. To prepare such complexes with different aliphatic dicarboxylate chain lengths was in an attempt to correlate this length factor, which influences the biological activity of the complexes, with fluorescence spectra, DNA cleavage and cytotoxic activity. The results indicate that the complexes bind to fish sperm DNA (FS-DNA) in an intercalative mode via fluorescence spectra, and the five complexes show different cleavage of supercoiled DNA, and then a cytotoxicity assay of these dinuclear palladium(II) complexes on human tumor cell lines was performed. In most of the cell lines, complex 5 (n=6) and 4 (n=5) showed much higher cytotoxicity than cis -platin. On the other hand, complex 3 (n=4) was found to be moderately active, and complex 1 (n=2), complex 2 (n=3) were found only marginally cytotoxic. Implications of these findings were discussed from a structure-activity relationship. [source] | ||||||||||||||||