Linked Life Data

19173620

Source:http://linkedlifedata.com/resource/pubmed/id/19173620

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2009-2-17
pubmed:abstractText
Most A/T specific heterocyclic diamidine derivatives need at least four A/T base pairs for tight binding to the DNA minor groove. Addition of a GC base pair to A/T sequences typically causes a large decrease in binding constant. The ability to target biologically important sequences of DNA could be significantly increased if compounds that could recognize A/T sites with an intervening GC base pair could be designed. The kinetoplast DNA sequence of parasitic microorganisms, for example, contains numerous three A/T binding sites that are separated by a single G. A series of compounds were prepared to target the AAAGTTT sequence as a model system for discovery of "G-jumpers". The new synthetic compounds have two aromatic-amidine groups for A/T recognition, and these are connected through an oxy-methylene linker to cross the GC. CD experiments indicated a minor groove binding mode, as expected, for these compounds. T(max), surface plasmon resonance, and isothermal titration calorimetry experiments revealed 1:1 binding to the AAAGTTT sequence with an affinity that depends on compound structure. Benzimidazole derivatives gave the strongest binding and had generally good solution properties. The binding affinities to the classical AATT sequence were similar to that for AAAGTTT for these extended compounds, but binding was weaker to the AAAGCTTT sequence with two intervening GC base pairs. Binding to both AAAGTTT and AATT was enthalpy driven for strong binding benzimidazole derivatives.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1520-4995
pubmed:author
pubmed:issnType
Electronic
pubmed:day
24
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1573-83
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Minor groove binding compounds that jump a gc base pair and bind to adjacent AT base pair sites.
pubmed:affiliation
Department of Chemistry, Georgia State University, P.O. Box 4098, Atlanta, Georgia 30302, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural