The synthesis and characterization of poly d(I-C) poly d(I-C)

Grant, Robert C.; Harwood, Steven J.; Wells, Robert D.

doi:10.1021/ja01018a060

Cited by 59 publications

(19 citation statements)

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“…The concentrations of the stock solutions were determined using the extinction coefficients: [ poly( dGdC)I2, E = 8400M-' cm-' at 254 nm33 and [poly(dAdT)],, E = 6600M-' cm-' at 262 nm. 34 The sodium salts of the mononucleotides 2'-deoxyguanosine-5'-mono-…”

Section: Methodsmentioning

confidence: 99%

The interaction of methylene blue, azure B, and thionine with DNA: Formation of complexes with polynucleotides and mononucleotides as model systems

1995

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Section: Methodsmentioning

confidence: 99%

The interaction of methylene blue, azure B, and thionine with DNA: Formation of complexes with polynucleotides and mononucleotides as model systems

1995

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“…(CGG⅐CCG) 73 was an XbaI-BamHI restriction fragment from plasmid pRW3691 and contained a total of 156 CG steps (including 10 from the triplet repeat flanking sequences) (47). d(I-C⅐I-C) ϳ7000 (48) give a stock solution of 500 M CG steps. Oligonucleotide concentrations were obtained by optical absorption on a Beckman DU 640 spectrophotometer using the extinction coefficients calculated from the known coefficients of the component nucleotides.…”

Section: Dnmt1 and S-(5ј-adenosyl)-l-[methyl-mentioning

confidence: 99%

Recombinant Human DNA (Cytosine-5) Methyltransferase

Bacolla¹,

Pradhan²,

Roberts³

et al. 1999

Journal of Biological Chemistry

115

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Initial velocity determinations were conducted with human DNA (cytosine-5) methyltransferase (DNMT1) on unmethylated and hemimethylated DNA templates in order to assess the mechanism of the reaction. Initial velocity data with DNA and S-adenosylmethionine (AdoMet) as variable substrates and product inhibition studies with methylated DNA and S-adenosylhomocysteine (AdoHcy) were obtained and evaluated as double-reciprocal plots. These relationships were linear for plasmid DNA, exon-1 from the imprinted small nuclear ribonucleoprotein-associated polypeptide N, (CGG⅐CCG) 12 , (m 5 CGG⅐CCG) 12 , and (CGG⅐CCG) 73 but were not linear for (CGG⅐Cm 5 CG) 12 . Inhibition by AdoHcy was apparently competitive versus AdoMet and uncompetitive/noncompetitive versus DNA at <20 M AdoMet. Addition of the product (methylated DNA) to unmethylated plasmid DNA increased V max(app) resulting in mixed stimulation and inhibition. Velocity equations indicated a two-step mechanism as follows: first, activation of DNMT1 by methylated DNA that bound to an allosteric site, and second, the addition of AdoMet and DNA to the catalytic site. The preference of DNMT1 for hemimethylated DNA may be the result of positive cooperativity of AdoMet binding mediated by allosteric activation by the methylated CG steps. We propose that this activation plays a role in vivo in the regulation of maintenance methylation.The genome of most organisms contains modified nucleotides including N 6 -methyladenine, N 4 -methylcytosine, and C 5 -methylcytosine (m 5 C) 1 (1-3). However, both the biological significance and the types of DNA methylation differ greatly between prokaryotes and eukaryotes. In prokaryotes, most modified bases participate in restriction-modification, a defense mechanism that protects the host from heterologous phage infection (4). In addition, N 6 -methyladenine plays a role in the initiation of DNA replication (5) and in post-replicative methyl-directed mismatch repair (6).In higher eukaryotes, DNA methylation is confined to m 5 C and is implicated in the regulation of development, genomic imprinting (7, 8), X chromosome inactivation, gene expression (9), and retrotransposon inactivation (10 -12). In mammals, the patterns of methylation are inherited from both parental genomes but are erased and reconstructed (de novo methylation) in somatic cells following implantation (13,14). Such patterns are then copied and maintained by hemimethylation of the daughter strands during semiconservative DNA synthesis in S phase (maintenance methylation) (15, 16). However, the mechanisms by which both de novo and maintenance methylation occur remain to be elucidated.Several DNA methyltransferases have been isolated from human and mouse (17-20), but it is not clear whether the de novo and maintenance methylations are carried out by separate proteins in vivo or whether both activities are shared by one or more enzymes (21-26). Nevertheless, a role for in vivo methylation has been established for isoforms of the human DNMT1 gene (27, 28) whose product, DNMT1, me...

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“…Their concentrations were determined applying the molar extinction coefficients per residue of 6,600, 6,900, 6,800 and 8,400 M -1 cm -1 respectively. 29,30 Natural DNAs solutions were prepared by suspending the lyophilized DNA overnight at 4°C in ETN buffer (10 mM TRIS, 1 mM EDTA, 6 mM NaCl pH 7.0). After one hour shaking, solutions were filtered through 5 µm Teflon filters (Millipore) and the ionic strength was adjusted to the desired value with NaCl.…”

Section: Methodsmentioning

confidence: 99%

Aminoacyl-analogues of mitoxantrone as novel DNA-damaging cytotoxic agents

Zagotto¹,

Sissi²,

Gatto³

et al. 2004

Arkivoc

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Anthracenedione derivatives are widely used structures to target DNA in chemotherapy. One of the major problem related to their use is their lack of sequence selectivity along the genome. With the aim of favoring recognition of selected DNA sequences, we synthesized four novel aminoacyl derivatives. Two side chains carrying aminoacid residues different for charge and chirality have been introduced at positions 1 and 4 of 5,8-dihydroxyanthracene-9,10-dione. An aminoethylamino spacer was inserted between the planar ring system and the selected aminoacid residues. Investigations in DNA binding properties of these new derivatives showed a large modulation of the drugs affinities for the nucleic acid depending upon the charge of the aminoacid used but irrespective of its chirality. However, as shown by topoisomerase II poisoning, prominent DNA-binding properties did not grant superior topoisomerase inhibition due mainly to template effect. In turn, aminoacid chirality plays a critical role in the in vitro cytotoxicity, L enantiomers being much more effective than D enantiomers. These findings suggest that conjugation of the anthracenedione moiety to aminoacids/peptides can be a valuable tool to selectively target cancer cells.

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The synthesis and characterization of poly d(I-C) poly d(I-C)

Cited by 59 publications

References 1 publication

The interaction of methylene blue, azure B, and thionine with DNA: Formation of complexes with polynucleotides and mononucleotides as model systems

The interaction of methylene blue, azure B, and thionine with DNA: Formation of complexes with polynucleotides and mononucleotides as model systems

Recombinant Human DNA (Cytosine-5) Methyltransferase

Aminoacyl-analogues of mitoxantrone as novel DNA-damaging cytotoxic agents

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