Linked Life Data

16119007

Source:http://linkedlifedata.com/resource/pubmed/id/16119007

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2005-8-25
pubmed:abstractText
Triple-stranded DNA structures have been implicated in a number of major biological processes, including the transcription and translation of a number of genes, as well as in the interaction of DNA with a number of proteins. Furthermore, antigene therapies under development are based on the recognition and binding of a single oligonucleotide strand to a double-stranded sequence, thus forming a triple helix. Triplex DNA formation is a relatively weak and temporary phenomenon; therefore, molecules that selectively bind to and stabilize triple helices may show a variety of novel biological effects. The biophysical and biological characterization of a series of antitumor polycyclic acridines that bind to triplex DNA is reported. These compounds, whose synthesis has been previously reported, have been tested for their interaction with both purine and pyrimidine type triple helices and compared with the relevant double-stranded DNA. As a pyrimidine triplex model we have used the T*AT sequence, which we have compared with the AT duplex, whereas the purine triplex oligonucleotide d[G3A4G3]*d[G3A4G3].d[C3T4C3] has been compared with the duplex d[G3A4G3].d[C3T4C3]. The compounds demonstrate various degrees of preferential binding to triplex DNA over normal duplex DNA, as measured by UV, fluorescence, circular dichroism, and thermal denaturation. Tri-substituted acridine derivatives demonstrated the highest affinity and ability to stabilize triplex DNA structures. Furthermore, structure/affinity analysis gives insights into the structural features that optimize affinity and selectivity for triplex DNA, and may play a role in their profile of antitumor activity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0965-0407
pubmed:author
pubmed:issnType
Print
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
95-105
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:16119007-Acridines, pubmed-meshheading:16119007-Amino Acid Motifs, pubmed-meshheading:16119007-Apoptosis, pubmed-meshheading:16119007-Buffers, pubmed-meshheading:16119007-Circular Dichroism, pubmed-meshheading:16119007-DNA, pubmed-meshheading:16119007-Hot Temperature, pubmed-meshheading:16119007-Humans, pubmed-meshheading:16119007-Hydrogen-Ion Concentration, pubmed-meshheading:16119007-Kinetics, pubmed-meshheading:16119007-Ligands, pubmed-meshheading:16119007-Macromolecular Substances, pubmed-meshheading:16119007-Mesylates, pubmed-meshheading:16119007-Models, Chemical, pubmed-meshheading:16119007-Neoplasms, pubmed-meshheading:16119007-Nucleic Acid Conformation, pubmed-meshheading:16119007-Nucleic Acids, pubmed-meshheading:16119007-Oligonucleotides, pubmed-meshheading:16119007-Protein Binding, pubmed-meshheading:16119007-Purines, pubmed-meshheading:16119007-Pyrimidines, pubmed-meshheading:16119007-Spectrometry, Fluorescence, pubmed-meshheading:16119007-Spectrophotometry, pubmed-meshheading:16119007-Temperature, pubmed-meshheading:16119007-Ultraviolet Rays
pubmed:year
2005
pubmed:articleTitle
Antitumor polycyclic acridines. Part 16. Triplex DNA as a target for DNA-binding polycyclic acridine derivatives.
pubmed:affiliation
Cancer Research UK Experimental Cancer Chemotherapy Research Group, Centre for Bio-molecular Sciences, School of Pharmacy, University of Nottingham, Nottingham, NG7 2RD, UK. s.missailidis@open.ac.uk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't