当前位置： SCI文献检索 > MOLECULAR PHARMACOLOGY期刊下所有文献 > DNA damage effects of a polyamide-CBI conjugate in SV40 virions.

DNA damage effects of a polyamide-CBI conjugate in SV40 virions.

Abstract：

:Polyamides are a class of synthetic molecules that exhibit high-affinity, sequence-specific reversible binding in the DNA minor groove but are incapable of inducing DNA damage. In cell-free systems, polyamides have been shown to regulate gene expression by activation, repression, and antirepression. However, effectiveness in cell culture has met with limited success and seems to be cell-dependent. By combining a polyamide with a moiety of a DNA-alkylating agent of the cyclopropylpyrroloindole (CPI) family, a conjugate molecule [polyamide 1-CBI (1-(chloromethyl)-5-hydroxyl-1,2-dihydro-3H-benz[e]indole) conjugate] capable of sequence-specific DNA alkylation was shown to exhibit cellular activity (i.e., cell-growth inhibition and cell-cycle arrest) in mammalian cells. These effects, however, occur at concentrations several orders of magnitude higher than those of its parent CPI agent adozelesin. In addition, 1-CBI is able to interact sequence-specifically with viral DNA and inhibit SV40 DNA replication in infected BSC-1 (African green monkey kidney epithelial) cells, albeit at a greatly reduced ability compared with its CPI parent. On the basis of results from previous studies, we tested whether pretreatment of virus with 1-CBI, compared with direct treatment of infected cells, would enhance its cellular activity. Therefore, using SV40 virions as a model system, we examined the ability of this conjugate molecule to penetrate SV40 virions and damage viral DNA. Our results demonstrate that 1-CBI is able to damage encapsidated SV40 DNA. Both DNA replication and virus production are effectively inhibited in a concentration-dependent manner after infection of BSC-1 cells with 1-CBI-pretreated virions. It is surprising that, unlike in mammalian cells, the relative activity of 1-CBI in SV40 virions is comparable with that of the highly cytotoxic CPI agent adozelesin. Because 1-CBI is able to efficiently penetrate virions and damage DNA, these findings may provide the framework for the development of polyamide-based antiviral agents with enhanced sequence-preference capabilities.

journal_name

Mol Pharmacol

journal_title

Molecular pharmacology

authors

Philips BJ,Chang AY,Dervan PB,Beerman TA

doi

10.1124/mol.104.006254

keywords:

subject

Has Abstract

pub_date

2005-03-01 00:00:00

pages

877-82

issue

3

eissn

0026-895X

issn

1521-0111

pii

mol.104.006254

journal_volume

67

pub_type

杂志文章

相关文献

MOLECULAR PHARMACOLOGY文献大全
  • Direct evidence for the existence and functional role of hyperreactive sulfhydryls on the ryanodine receptor-triadin complex selectively labeled by the coumarin maleimide 7-diethylamino-3-(4'-maleimidylphenyl)-4-methylcoumarin.

    abstract：:The fluorogenic sulfhydryl probe 7-diethylamino-3-(4'-maleimidylphenyl)-4-methylcoumarin (CPM) (1-50 nM) is used to characterize the functional role and location of highly reactive thiol groups on the ryanodine-sensitive Ca2+ release channel complex [i.e., ryanodine receptors (RyRs)] of skeletal and cardiac junctional...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Liu G,Abramson JJ,Zable AC,Pessah IN

    更新日期：1994-02-01 00:00:00

  • Are alpha9alpha10 nicotinic acetylcholine receptors a pain target for alpha-conotoxins?

    abstract：:The synthetic alpha-conotoxin Vc1.1 is a small disulfide bonded peptide currently in development as a treatment for neuropathic pain. Unlike Vc1.1, the native post-translationally modified peptide vc1a does not act as an analgesic in vivo in rat models of neuropathic pain. It has recently been proposed that the primar...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.107.040568

    authors： Nevin ST,Clark RJ,Klimis H,Christie MJ,Craik DJ,Adams DJ

    更新日期：2007-12-01 00:00:00

  • PDZ Protein Regulation of G Protein-Coupled Receptor Trafficking and Signaling Pathways.

    abstract：:G protein-coupled receptors (GPCRs) contribute to the regulation of every aspect of human physiology and are therapeutic targets for the treatment of numerous diseases. As a consequence, understanding the myriad of mechanisms controlling GPCR signaling and trafficking is essential for the development of new pharmacolo...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章,评审

    doi：10.1124/mol.115.098509

    authors： Dunn HA,Ferguson SS

    更新日期：2015-10-01 00:00:00

  • Solubilization and characterization of pituitary thyrotropin-releasing hormone receptors.

    abstract：:Thyrotropin-releasing hormone (TRH) receptors were solubilized from a rat pituitary tumor cell line, GH4C1, with digitonin. Convenient assays were developed based on the ability of hydroxylapatite and polyethyleneimine-soaked glass fiber filters to adsorb the solubilized [3H]methyl-TRH-receptor complex but not free [3...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Phillips WJ,Hinkle PM

    更新日期：1989-04-01 00:00:00

  • Effects of pertussis toxin on cAMP and cGMP responses to carbamylcholine in N1E-115 neuroblastoma cells.

    abstract：:As noted previously, in N1E-115 neuroblastoma cells, carbamylcholine, a muscarinic cholinergic agonist, increased cGMP over 15-fold and decreased basal and prostaglandin E1 (PGE1)-stimulated cAMP content. In contrast to the stimulatory effects of PGE1 on cAMP, which were immediate, the carbamylcholine-induced decrease...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Bruni P,Burns DL,Hewlett EL,Moss J

    更新日期：1985-08-01 00:00:00

  • Inhibition of the multidrug resistance protein 1 (MRP1) by peptidomimetic glutathione-conjugate analogs.

    abstract：:Inhibition of multidrug resistance protein 1 (MRP1) mediated cytostatic drug efflux might be useful in the treatment of drug resistant tumors. Because the glutathione (GSH) conjugate of ethacrynic acid (EA), GS-EA, is a good substrate of MRP1, GS-EA derivatives are expected to be good inhibitors of MRP1. To study stru...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.62.5.1160

    authors： Burg D,Wielinga P,Zelcer N,Saeki T,Mulder GJ,Borst P

    更新日期：2002-11-01 00:00:00

  • Valproic acid inhibits angiogenesis in vitro and in vivo.

    abstract：:Valproic acid (VPA) is a widely used antiepileptic agent that is undergoing clinical evaluation for anticancer therapy. We assessed the effects of VPA on angiogenesis in vitro and in vivo. In human umbilical vein endothelial cells, therapeutically relevant concentrations of VPA (0.25 to 1 mM) inhibited proliferation, ...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.65.3.520

    authors： Michaelis M,Michaelis UR,Fleming I,Suhan T,Cinatl J,Blaheta RA,Hoffmann K,Kotchetkov R,Busse R,Nau H,Cinatl J Jr

    更新日期：2004-03-01 00:00:00

  • Pivotal role for the cytoplasmic carboxyl-terminal tail of a nonmammalian gonadotropin-releasing hormone receptor in cell surface expression, ligand binding, and receptor phosphorylation and internalization.

    abstract：:The gonadotropin-releasing hormone receptor (GnRH-R) of the African catfish couples to phospholipase C and belongs to the large family of G protein-coupled receptors. We recently demonstrated that removal of the carboxyl-terminal tail (S331-Q379) from the catfish GnRH-R results in a loss of agonist binding; the curren...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.56.6.1229

    authors： Blomenröhr M,Heding A,Sellar R,Leurs R,Bogerd J,Eidne KA,Willars GB

    更新日期：1999-12-01 00:00:00

  • S-nitrosylating agents: a novel class of compounds that increase cystic fibrosis transmembrane conductance regulator expression and maturation in epithelial cells.

    abstract：:The endogenous bronchodilator, S-nitrosoglutathione (GSNO), increases expression, maturation, and function of both the wild-type and the DeltaF508 mutant of the cystic fibrosis transmembrane conductance regulatory protein (CFTR). Though transcriptional mechanisms of action have been identified, GSNO seems also to have...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.106.023242

    authors： Zaman K,Carraro S,Doherty J,Henderson EM,Lendermon E,Liu L,Verghese G,Zigler M,Ross M,Park E,Palmer LA,Doctor A,Stamler JS,Gaston B

    更新日期：2006-10-01 00:00:00

  • Beta-adrenergic desensitization reduces the sensitivity of adenylate cyclase for magnesium in permeabilized lymphocytes.

    abstract：:Magnesium modulates hormone-sensitive adenylate cyclase activation. In the present studies, we have examined the magnesium requirement of beta-adrenergic-stimulated adenylate cyclase activity in permeabilized human lymphocytes. Following isoproterenol pretreatment, under conditions that lead to homologous beta-adrener...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Feldman RD

    更新日期：1989-03-01 00:00:00

  • Interpretation of binding curves obtained with high receptor concentrations: practical aid for computer analysis.

    abstract：:Typical equilibrium binding experiments cannot be quantitatively analyzed on the basis of classical mathematical equations when the receptor concentration is so high that a significant fraction of the added radioligand concentration is in the bound form. In this paper, the appropriate equations are derived and used in...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Swillens S

    更新日期：1995-06-01 00:00:00

  • Differential activation of human gastrin-releasing peptide receptor-mediated responses by bombesin analogs.

    abstract：:To enable the detailed pharmacological characterization of five bombesin (BN) analogs with respect to the human gastrin-releasing peptide (GRP) receptor, we ectopically expressed the receptor in BALB/3T3 cells. In such cells (termed GR1 cells), GRP stimulated DNA synthesis and Ca2+ mobilization. Two of these analogs, ...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Wu JM,Hoang DO,Feldman RI

    更新日期：1995-04-01 00:00:00

  • Binding of two anthranilic acid derivatives to human albumin, erythrocytes, and lipoproteins: evidence for glafenic acid high affinity binding.

    abstract：:The binding of two anthranilic acid derivatives, glafenic and floctafenic acids, to human erythrocytes and plasma proteins has been investigated in vitro by equilibrium dialysis. Despite their close chemical structures it was shown that the binding of the two compounds to serum albumin, lipoproteins, and erythrocytes ...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Albengres E,Urien S,Riant P,Marcel GA,Tillement JP

    更新日期：1987-03-01 00:00:00

  • Elucidating the molecular basis of action of a classic drug: guanidine compounds as inhibitors of voltage-gated potassium channels.

    abstract：:Guanidine and its alkyl analogs stimulate the neuromuscular junction presynaptically by inhibiting voltage-gated potassium (Kv) channels, leading to enhanced release of acetylcholine in the synaptic cleft. This stimulatory effect of guanidine underlies its use in the therapy for the neuromuscular diseases myasthenic s...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.111.074989

    authors： Kalia J,Swartz KJ

    更新日期：2011-12-01 00:00:00

  • CYP2C8 Is a Novel Target of Peroxisome Proliferator-Activated Receptor α in Human Liver.

    abstract：:Human cytochrome P450 (CYP) 2C enzymes metabolize ∼30% of clinically prescribed drugs and various environmental chemicals. CYP2C8, an important member of this subfamily, metabolizes the anticancer drug paclitaxel, certain antidiabetic drugs, and endogenous substrates, including arachidonic acid, to physiologically act...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.115.100255

    authors： Makia NL,Goldstein JA

    更新日期：2016-01-01 00:00:00

  • Differential spatial approximation between cholecystokinin residue 30 and receptor residues in active and inactive conformations.

    abstract：:Understanding the structures of active and inactive agonist- and antagonist-bound receptor complexes is of great interest. In this work, we focus on position 30 of cholecystokinin (CCK) and its spatial approximation with the type A CCK receptor. For this, we developed two photoaffinity labeling probes, replacing the n...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.105.012179

    authors： Dong M,Hadac EM,Pinon DI,Miller LJ

    更新日期：2005-06-01 00:00:00

  • Antagonist binding properties of five cloned muscarinic receptors expressed in CHO-K1 cells.

    abstract：:A family of five cholinergic muscarinic receptor genes (m1, m2, m3, m4, and m5) has recently been identified and cloned. In order to investigate the pharmacological properties of the individual muscarinic receptors, we have transfected each of these genes into Chinese hamster ovary cells (CHO-K1) and have established ...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Buckley NJ,Bonner TI,Buckley CM,Brann MR

    更新日期：1989-04-01 00:00:00

  • The human heart beta-adrenergic receptors. I. Heterogeneity of the binding sites: presence of 50% beta 1- and 50% beta 2-adrenergic receptors.

    abstract：:Beta-adrenergic receptors were characterized in a particulate fraction of human auricles obtained from patients operated upon for coronary insufficiency or valvular disease. [125I] Hydroxybenzylpindolol binding was evaluated in terms of kinetics; KD and Bmax values; and inhibition of binding in the presence of 10 micr...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Robberecht P,Delhaye M,Taton G,De Neef P,Waelbroeck M,De Smet JM,Leclerc JL,Chatelain P,Christophe J

    更新日期：1983-09-01 00:00:00

  • Induction of the cytochrome P450 gene CYP26 during mucous cell differentiation of normal human tracheobronchial epithelial cells.

    abstract：:In this study, the expression of CYP26 is examined in relation to retinoid-induced mucosecretory differentiation in human tracheobronchial epithelial (HTBE) cells and compared with that in human lung carcinoma cell lines. In HTBE cells, retinoic acid (RA) inhibits squamous differentiation and induces mucous cell diffe...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.58.3.483

    authors： Kim SY,Adachi H,Koo JS,Jetten AM

    更新日期：2000-09-01 00:00:00

  • Involvement of neuronal cannabinoid receptor CB1 in regulation of bone mass and bone remodeling.

    abstract：:The CB1 cannabinoid receptor has been implicated in the regulation of bone remodeling and bone mass. A high bone mass (HBM) phenotype was reported in CB1-null mice generated on a CD1 background (CD1(CB1-/-) mice). By contrast, our preliminary studies in cb1-/- mice, backcrossed to C57BL/6J mice (C57(CB1-/-) mice), rev...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.106.026435

    authors： Tam J,Ofek O,Fride E,Ledent C,Gabet Y,Müller R,Zimmer A,Mackie K,Mechoulam R,Shohami E,Bab I

    更新日期：2006-09-01 00:00:00

  • Strong activation of ether-à-go-go-related gene 1 K+ channel isoforms by NS1643 in human embryonic kidney 293 and Chinese hamster ovary cells.

    abstract：:Two different mechanisms leading to increased current have been described for the small-molecule human ether-à-go-go-related gene (herg) activator NS1643 [1,3-bis-(2-hydroxy-5-trifluoromethylphenyl)-urea]. On herg1a channels expressed in Xenopus laevis oocytes, it mainly acts via attenuation of inactivation and for ra...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.111.071621

    authors： Schuster AM,Glassmeier G,Bauer CK

    更新日期：2011-11-01 00:00:00

  • Histidine residues 912 and 913 in protein associated with Myc are necessary for the inhibition of adenylyl cyclase activity.

    abstract：:We reported previously that protein associated with Myc (PAM) interacts with the C2 domain of type V adenylyl cyclase (ACV-C2) and that purified PAM is a potent inhibitor of Galphas-stimulated ACV activity (J Biol Chem 276:47583-47589, 2001). The present study was conducted to identify the region in PAM that inhibits ...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.104.005355

    authors： Gao X,Patel TB

    更新日期：2005-01-01 00:00:00

  • Tubulin-Binding 3,5-Bis(styryl)pyrazoles as Lead Compounds for the Treatment of Castration-Resistant Prostate Cancer.

    abstract：:The microtubule-binding taxanes, docetaxel and cabazitaxel, are administered intravenously for the treatment of castration-resistant prostate cancer (CRPC) as the oral administration of these drugs is largely hampered by their low and highly variable bioavailabilities. Using a simple, rapid, and environmentally friend...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.119.118539

    authors： Liao VWY,Kumari A,Narlawar R,Vignarajan S,Hibbs DE,Panda D,Groundwater PW

    更新日期：2020-06-01 00:00:00

  • Phosphatidylinositol 3,4,5-triphosphate-dependent Rac exchanger 1 (P-Rex-1), a guanine nucleotide exchange factor for Rac, mediates angiogenic responses to stromal cell-derived factor-1/chemokine stromal cell derived factor-1 (SDF-1/CXCL-12) linked to Rac

    abstract：:Stromal cell-derived factor-1 (SDF-1/CXCL-12) and vascular endothelial growth factor (VEGF), which can be secreted by hypoxic tumors, promote the generation of new blood vessels. These potent angiogenic factors stimulate endothelial cell migration via the activation of Rho GTPases and the phosphatidylinositol 3-kinase...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.109.060400

    authors： Carretero-Ortega J,Walsh CT,Hernández-García R,Reyes-Cruz G,Brown JH,Vázquez-Prado J

    更新日期：2010-03-01 00:00:00

  • Mpl ligand increases P2Y1 receptor gene expression in megakaryocytes with no concomitant change in platelet response to ADP.

    abstract：:The P2Y(1) receptor is responsible for the initiation of platelet aggregation in response to ADP and plays a key role in thrombosis. Although this receptor is expressed early in the platelet lineage, the regulation of its expression during megakaryocyte differentiation is unknown. In the mouse megakaryocytic cell line...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.60.5.1112

    authors： Hechler B,Toselli P,Ravanat C,Gachet C,Ravid K

    更新日期：2001-11-01 00:00:00

  • Identification of potential pharmacological targets by analysis of the comprehensive G protein-coupled receptor repertoire in the four cardiac chambers.

    abstract：:Cardiac function is regulated by many hormones and neurotransmitters that exert their physiological effects through the activation of G protein-coupled receptors (GPCRs). Identification of new GPCRs that might display a specific pattern of expression within the heart and differentially regulate specific cardiac functi...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.108.054155

    authors： Moore-Morris T,Varrault A,Mangoni ME,Le Digarcher A,Negre V,Dantec C,Journot L,Nargeot J,Couette B

    更新日期：2009-05-01 00:00:00

  • Regulation of the CYP1A1 gene by 2,3,7,8-tetrachlorodibenzo-p-dioxin but not by beta-naphthoflavone or 3-methylcholanthrene is altered in hepatitis C virus replicon-expressing cells.

    abstract：:Exposure to hepatitis C virus (HCV) can lead to the development of cirrhosis and hepatocellular carcinoma. To examine the effects of long-term HCV infection on hepatic cytochrome P450 1A1 (CYP1A1) expression and function, we used a human hepatoma cell line expressing the HCV subgenomic replicon (Huh.8) to evaluate CYP...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.106.024125

    authors： Anderson GR,Hasan A,Yin H,Qadri I,Quattrochi LC

    更新日期：2006-09-01 00:00:00

  • Effects of morpholinyl doxorubicins, doxorubicin, and actinomycin D on mammalian DNA topoisomerases I and II.

    abstract：:The effect of cyanomorpholinyldoxorubicin, morpholinyldoxorubicin, doxorubicin, and Actinomycin D were studied on purified mouse leukemia (L1210) DNA topoisomerases I and II. DNA unwinding and cross-linking were also studied. It was found that 1) morpholinyldoxorubicin, cyanomorpholinyldoxorubicin, and Actinomycin D (...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Wassermann K,Markovits J,Jaxel C,Capranico G,Kohn KW,Pommier Y

    更新日期：1990-07-01 00:00:00

  • 9-beta-D-arabinofuranosyl-2-fluoroadenine inhibits expression of vascular endothelial growth factor through hypoxia-inducible factor-1 in human ovarian cancer cells.

    abstract：:Ovarian cancer is the leading cause of death from gynecological malignancy and has the worst prognosis of all gynecological cancers. Vascular endothelial growth factor (VEGF) plays an important role in ovarian cancer development. 9-beta-D-Arabinofuranosyl-2-fluoroadenine (Fara-A), a nucleotide analog, is frequently us...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.66.1.178

    authors： Fang J,Cao Z,Chen YC,Reed E,Jiang BH

    更新日期：2004-07-01 00:00:00

  • Mismatch repair of cis-diamminedichloroplatinum(II)-induced DNA damage.

    abstract：:Because cytotoxicity by an alkylating agent such as N-methyl-N'-nitrosoguanidine is markedly increased in adenine methylase-deficient dam-3 Escherichia coli, it was of interest to assess whether mismatch repair was similarly important in the repair of DNA damage induced by cis-diamminedichloroplatinum(II) (CDDP). The ...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Fram RJ,Cusick PS,Wilson JM,Marinus MG

    更新日期：1985-07-01 00:00:00