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  Subjects -> BIOLOGY (Total: 3003 journals)
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BIOLOGY (1427 journals)                  1 2 3 4 5 6 7 8 | Last

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Arthropods     Open Access   (Followers: 1)
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        1 2 3 4 5 6 7 8 | Last

Journal Cover Advances in DNA Sequence-Specific Agents
  [5 followers]  Follow
    
   Full-text available via subscription Subscription journal
   ISSN (Print) 1067-568X
   Published by Elsevier Homepage  [3043 journals]
  • List of contributors
    • Abstract: 2002
      Publication year: 2002
      Source:Advances in DNA Sequence-Specific Agents, Volume 4



      PubDate: 2012-12-16T22:34:44Z
       
  • Preferential damage to defined regions of genomic DNA by AT-specific
           anticancer drugs
    • Abstract: 2002
      Publication year: 2002
      Source:Advances in DNA Sequence-Specific Agents, Volume 4

      A non-random distribution of DNA lesions in various domains of the human genome may be important for the selectivity of antiproliferative action of anticancer drugs. Recent investigations explored the determinants of region-specific damage to cellular DNA in cancer cells by comparing highly AT-specific drugs (bizelesin, adozelesin, U-78779, and tallimustine) to a relatively non-specific drug, cisplatin. These studies consistently show that sequence specificity at the nucleotide level and a long-range distribution of drug binding motifs analyzed “in silico” predict well the actual relative vulnerability of specific regions to various drugs. Bizelesin is the first small molecular weight anticancer drug demonstrated to preferentially damage specific regions in cellular DNA. Bizelesin is region specific because its binding motif is non-randomly distributed, with clusters in long (200–1000 bp) islands of AT-rich DNA. A substantial specificity of this drug at the nucleotide level is an important and necessary factor to accomplish region-specific damage. The less specific adozelesin targets similar regions as bizelesin but with only a marginal preference over other areas of the genome. Cisplatin is not a region-specific drug, due to its low specificity of DNA recognition and the omnipresence of its potential binding sites. High specificity at the nucleotide level, however, is per se insufficient for region specificity. Tallimustine is not region specific, despite the very high sequence specificity. Paradoxically, the highly specific, and accordingly infrequent, tallimustine sites are distributed throughout the genome nearly randomly, resembling the distribution of much less specific (and more numerous) lesions by cisplatin. The consequences of DNA lesions in AT-islands targeted by bizelesin seem to be dramatically more lethal than non region-specific lesions by tallimustine and cisplatin. The reviewed findings provide a proof of principle that targeting of critical repetitive sequences (not necessarily coding regions), which allow for clustering of drug binding motif, can be the paradigm for region specificity of small molecular weight agents. The notion of regional drug targeting should be recognized as an essential extension of the rational design of sequence-specific drugs.

      PubDate: 2012-12-16T22:34:44Z
       
  • DNA-alkylating events associated with nitrogen mustard based anticancer
           drugs and the metabolic byproduct Acrolein
    • Abstract: 2002
      Publication year: 2002
      Source:Advances in DNA Sequence-Specific Agents, Volume 4

      The nitrogen mustard anticancer drugs are widely used for treating many forms of cancer. However, a number of toxic side effects, including secondary tumors, limit their clinical utility. There is strong evidence that the effectiveness for killing cancer cells (cytotoxicity) of these drugs is directly related to the ability of their metabolites to form interstrand DNA crosslinks. These crosslinks are formed by the sequential alkylation of two bases on complementary DNA strands. Other products, including monoalkylated adducts and intrastrand crosslinks are much less cytotoxic, and can mutate the DNA in normal cells leading to the formation of secondary tumors. The nitrogen mustards have a complex DNA-alkylation chemistry. They form monoalkylation adducts at a number of different sites on DNA and the predominant lesions vary between mustards and are strongly modulated by conjugation with DNA-targeting groups including intercalators, minor groove binders, and triplex-forming DNA oligomers. Only a small fraction of the DNA-alkylation events proceed to the formation of the therapeutically useful, highly cytotoxic crosslinks. For this reason there is considerable ongoing research to improve the efficiency of crosslink formation, and reduce the mutagenic effects of the other mustard-induced lesions. The phosphoramide mustard prodrugs including cyclophosphamide and ifosfamide, produce acrolein as a metabolic byproduct. Like the mustards themselves, acrolein has a complex DNA-alkylation chemistry, leading to a diversity of DNA adducts.

      PubDate: 2012-12-16T22:34:44Z
       
  • Molecular basis for recognition and binding of specific DNA sequences by
           calicheamicin and duocarmycin
    • Abstract: 2002
      Publication year: 2002
      Source:Advances in DNA Sequence-Specific Agents, Volume 4



      PubDate: 2012-12-16T22:34:44Z
       
  • Enediyne antibiotic neocarzinostatin as a radical-based probe of bulged
           structures in nucleic acids
    • Abstract: 2002
      Publication year: 2002
      Source:Advances in DNA Sequence-Specific Agents, Volume 4



      PubDate: 2012-12-16T22:34:44Z
       
  • Sequence-specific DNA binding by short peptides
    • Abstract: 2002
      Publication year: 2002
      Source:Advances in DNA Sequence-Specific Agents, Volume 4



      PubDate: 2012-12-16T22:34:44Z
       
  • Equilibrium and kinetic quantitative DNase I footprinting
    • Abstract: 2002
      Publication year: 2002
      Source:Advances in DNA Sequence-Specific Agents, Volume 4



      PubDate: 2012-12-16T22:34:44Z
       
  • List of contributors
    • Abstract: 1998
      Publication year: 1998
      Source:Advances in DNA Sequence-Specific Agents, Volume 3



      PubDate: 2012-12-16T22:34:44Z
       
  • Introduction to DNA sequence-specific agents
    • Abstract: 1998
      Publication year: 1998
      Source:Advances in DNA Sequence-Specific Agents, Volume 3



      PubDate: 2012-12-16T22:34:44Z
       
  • Sequence-specific poisons of type II DNA topoisomerases
    • Abstract: 1998
      Publication year: 1998
      Source:Advances in DNA Sequence-Specific Agents, Volume 3



      PubDate: 2012-12-16T22:34:44Z
       
  • Topoisomerase I-targeting drugs New developments in cancer pharmacology
    • Abstract: 1998
      Publication year: 1998
      Source:Advances in DNA Sequence-Specific Agents, Volume 3



      PubDate: 2012-12-16T22:34:44Z
       
  • DNA sequence recognition altered bis-benzimidazole minor-groove binders
    • Abstract: 1998
      Publication year: 1998
      Source:Advances in DNA Sequence-Specific Agents, Volume 3



      PubDate: 2012-12-16T22:34:44Z
       
  • Sequence-specific recognition and modification of double-helical DNA by
           minor-groove binding conjugates structurally related to netropsin and
           distamycin
    • Abstract: 1998
      Publication year: 1998
      Source:Advances in DNA Sequence-Specific Agents, Volume 3



      PubDate: 2012-12-16T22:34:44Z
       
  • New developments in the use of nitrogen mustard alkylating agents as
           anticancer drugs
    • Abstract: 1998
      Publication year: 1998
      Source:Advances in DNA Sequence-Specific Agents, Volume 3



      PubDate: 2012-12-16T22:34:44Z
       
  • DNA binding of nonclassical platinum antitumor complexes
    • Abstract: 1998
      Publication year: 1998
      Source:Advances in DNA Sequence-Specific Agents, Volume 3

      Bifunctional binding of platinum complexes to DNA is considered essential for manifestation of antitumor activity. Studies on direct analogues of cis-DDP confirm that all cis-[PtX2(amine)2] complexes will produce a similar array of adducts with similar consequences. This fact may well be a reason for the similarity in clinical profile of those analogues which have entered clinical trials. On the other hand, work on dinuclear platinum and trans-platinum complexes indicate that complexes structurally different to cis-DDP and acting on DNA in a manner distinct to the clinically used agent may display an altered spectrum of antitumor activity. A rich array of new structures has been discovered worthy of further exploration to develop new platinum complexes genuinely complementary to the currently used drugs.109

      PubDate: 2012-12-16T22:34:44Z
       
  • Kedarcidin and maduropeptin Two novel antitumor chromoproteins with
           selective protease activity and DNA cleaving properties
    • Abstract: 1998
      Publication year: 1998
      Source:Advances in DNA Sequence-Specific Agents, Volume 3



      PubDate: 2012-12-16T22:34:44Z
       
  • Antisense- and antigene-based drug design strategies in oncology
    • Abstract: 1998
      Publication year: 1998
      Source:Advances in DNA Sequence-Specific Agents, Volume 3



      PubDate: 2012-12-16T22:34:44Z
       
  • Sequence-specific recognition of double-stranded DNA by peptide nucleic
           acids
    • Abstract: 1998
      Publication year: 1998
      Source:Advances in DNA Sequence-Specific Agents, Volume 3



      PubDate: 2012-12-16T22:34:44Z
       
  • List of contributors
    • Abstract: 1996
      Publication year: 1996
      Source:Advances in DNA Sequence-Specific Agents, Volume 2



      PubDate: 2012-12-16T22:34:44Z
       
  • Calorimetric studies of drug-DNA interactions
    • Abstract: 1996
      Publication year: 1996
      Source:Advances in DNA Sequence-Specific Agents, Volume 2

      Calorimetric techniques are powerful tools for the study of the energetics involved in the conformational plasticity of nucleic acids and in their interaction with ligands. The techniques of ITC and DSC, described here, provide us with the universal measurement of the heat associated in these reactions and allows dissection of the free energy terms into their corresponding enthalpic and entropic contributions. They also provide additional extrathermodynamic data such as, but not limited to, stoichiometry of complexes, ion binding, and cooperativity. In this review we have tried to give the reader a brief overview and discussion on how to apply calorimetric techniques for the understanding of ligand binding to DNA by using typical examples on the ligand mode of binding, ligand sequence specificity, the novel binding of ligands to hairpin loops, and the interaction of ligands to nonclassical DNA structures of current biological importance.

      PubDate: 2012-12-16T22:34:44Z
       
  • Molecular modeling of drug-DNA interactions Facts and fantasies
    • Abstract: 1996
      Publication year: 1996
      Source:Advances in DNA Sequence-Specific Agents, Volume 2



      PubDate: 2012-12-16T22:34:44Z
       
  • X-ray crystallographic and NMR structural studies of anthracycline
           anticancer drugs Implication in drug design
    • Abstract: 1996
      Publication year: 1996
      Source:Advances in DNA Sequence-Specific Agents, Volume 2

      Crystal structure analysis of several complexes between important anthracycline drugs and DNA oligonucleotides affords us valuable information for understanding the role of various functional groups of the drug molecules. Moreover, the excellent agreement between the crystal and solution structures shown in the analyses of the Ng-CGTACG complex showed that a quantitative treatment of NOE data is an effective alternate way of producing a reliable three-dimensional structure of drug-DNA complexes. Aclacinomycins A and B, complexed to DNA by the same procedure, provided us with a structure that is not yet available from X-ray crystallography. Similar analyses of other drugs, such as arugomycin,57 will be useful in our understanding of the function of anthracycline antibiotics in general. The structural results also offer some clues for the design of new and unique classes of potential drugs. For example, our preliminary data on the nature of the drug-DNA cross-link suggest that such a complex has several potential beneficial properties as an anticancer drug: o 1. The conjugate can be prepared readily and efficiently with very high loading of the drug [to a maximum of one DOX per three base pairs for poly(dG-dC)]. 2. The conjugate may be long-lived in the blood stream, serving as a slow-releasing drug reservoir. 3. The cytotoxic agent is hidden in the DNA lattice, avoiding the attack by enzyme that causes the formation of the free radical species of DOX. This may reduce the cardiotoxicity side effect. 4. If the conjugate can be picked up by the cancer cells directly, it may be effective against resistant cells. 5. The conjugate should be resistant to nuclease, since the DNA conformation is severely distorted by the intercalated drug. 6. A sequence-specific DNA-DOX adduct may be prepared, as long as some guanine nucleotides are present. We believe that continuing structural studies on many drugs bound to their receptors will be extremely fruitful in guiding the design of new drugs.

      PubDate: 2012-12-16T22:34:44Z
       
  • Transcriptional assay for probing molecular aspects of drug-DNA
           interactions
    • Abstract: 1996
      Publication year: 1996
      Source:Advances in DNA Sequence-Specific Agents, Volume 2

      An in vitro transcription assay of drug-DNA interactions has been developed largely on the basis of the stable lac-UV5-initiated transcription complex. This system comprises a synchronized population of radiolabeled nascent RNA ten nucleotides long. Reaction of drugs with this initiated transcription complex, followed by elongation of the nascent RNA by E. coli RNA polymerase, reveals blockages at drug sites. From these blockages it is possible to obtain four features of the drug-DNA interaction: the sequence of preferred drug binding sites; the relative drug occupancy at each site; the drug dissociation rate at each site; and the probability of drug-induced termination of transcription at each site. The unidirectional transcription assay has also been extended to a two-promoter, counter-directed system, which yields a bidirectional transcriptional footprint of drug sites. The transcription assay has recently been applied to in vitro eukaryotic systems in which drug-induced block-ages of RNA polymerase II reveal drug binding sites and the capacity of elongation factors to influence the effect of drugs at these sites.

      PubDate: 2012-12-16T22:34:44Z
       
  • Molecular recognition of DNA by Daunorubicin
    • Abstract: 1996
      Publication year: 1996
      Source:Advances in DNA Sequence-Specific Agents, Volume 2



      PubDate: 2012-12-16T22:34:44Z
       
  • Covalent interactions of ethidium and actinomycin D with nucleic acids
           Photoaffinity labeling of DNA
    • Abstract: 1996
      Publication year: 1996
      Source:Advances in DNA Sequence-Specific Agents, Volume 2



      PubDate: 2012-12-16T22:34:44Z
       
  • DNA binding of dinuclear platinum complexes
    • Abstract: 1996
      Publication year: 1996
      Source:Advances in DNA Sequence-Specific Agents, Volume 2

      Bifunctional binding of platinum complexes to DNA is considered essential for manifestation of antitumor activity. The studies on [{PtCl(NH3)2}2H2N(CH2)4NH2]2+ show that complexes structurally different to cis-DDP and acting on DNA in a manner distinct from the clinically used agent may display an altered spectrum of antitumor activity. Table 2 summarizes how bifunctional binding may be systematically modified by bis(platinum) complexes to give lesions that are structurally distinct from the cis-DDP-DNA adducts, thus affecting both conformational changes and sequence specificity. Inhibition of both DNA synthesis and transcription has been implicated as the locus of cisplatin action.28,80,81 The clinical efficacy of cis-DDP may be eventually due to differential repair of the lesions formed, a point that is also important in development of cis-DDP resistance. The location of adducts within specific genes is also expected to influence these factors to a greater extent than formation of adducts in nontranscribing regions of DNA.46 Randomly platinated DNA is a substrate for the UVrABC repair system,67,82 but individual adducts are not all excised with equal efficiency.83 Emphasizing that the structurally different lesions of cis-DDP produce different cellular responses is the enhanced mutagenicity of the d(ApG) adduct in comparison to the d(GpG) adduct.84,85 Likewise, the structural features of the bis(platinum)-DNA adducts will be expected to have further biological consequences such as inhibition of DNA synthesis or altered susceptibility to DNA repair. The altered profile of Pt-DNA binding described here confirms that useful biological activity is not restricted to direct analogues of the cis-DDP structure. The potential for systematic variation of DNA-binding properties within the dinuclear structure affords the promise for rational drug design and more specific inhibition of critical cellular and biochemical targets.

      PubDate: 2012-12-16T22:34:44Z
       
  • DNA sequence selectivity of the pyrrole-derived, bifunctional alkylating
           agents
    • Abstract: 1996
      Publication year: 1996
      Source:Advances in DNA Sequence-Specific Agents, Volume 2

      Several of the substances used in the treatment of cancer in humans are bifunctional alkylating agents. The biological target of these substances is believed to be DNA; interstrand or intrastrand DNA-DNA cross-linking is likely to be important in this regard. This chapter describes the DNA-DNA cross-linking reactions of a family of bifunctional electrophiles that show remarkable similarity with regard to the nucelotide sequence, at which they form interstrand cross-links [5′-d(CG)] and the atomic sites that are linked (N-2 of deoxyguanosines on opposing strands). These substances include reductively activated mitomycin C, oxidatively activated pyrrolizidine alkaloids,2,3- and 3,4-bis(acetoxymethyl)-1-methylpyrrole, a distamycin conjugate of 2,3-bis(hydroxymethyl)-1-methylpyrrole, FR900482, and FR66979. The feature that links these structurally diverse substances to one another is the presence of, or the ability to form, a pyrrole ring substituted at adjacent carbons with masked electrophilic centers. This geometry is an excellent match to the nucleophilic sites on N-2 of deoxyguanosines at the duplex sequence 5′-d(CG), possibly accounting for some or all of the atomic site and sequence specificities of these substances.

      PubDate: 2012-12-16T22:34:44Z
       
 
 
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