Linked Life Data

7679636

Source:http://linkedlifedata.com/resource/pubmed/id/7679636

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1993-3-23
pubmed:abstractText
The interaction of Hoechst 33258 with the minor groove of the A + T-rich DNA duplex d(GGTAATTACC)2 has been investigated in solution by two-dimensional 1H-NMR spectroscopy. Many intermolecular NOEs define the position and orientation of the Hoechst molecule at the centre of the duplex, binding to a single site located within the minor groove of the AATT sequence. This is despite the opportunity for Hoechst 33258 to bind to as many as five unique sites containing the minimum requirement of three consecutive A.T base pairs. All intermolecular NOEs are detected between protons on the concave edge of Hoechst, many with the adenine H2s on the floor of the minor groove. The NOEs are consistent with interproton distances measured within a partially restrained energy-minimised structure of the complex. The AATT sequence provides the key recognition features for tight binding, including a particularly narrow minor groove, with no evidence for the partial G.C specificity previously proposed to be necessary to accommodate the bulky N-methylpiperazine ring. While chemical exchange cross-peaks between symmetry-related adenine H2s on opposite strands of the duplex identify a very slow rate of dissociation of the drug from the complex at 298 K (exchange rate approximately 1.2 s-1). Averaging of chemical shifts in the phenyl ring of Hoechst 33258 are indicative of rapid ring-flipping motions in the bound state.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0014-2956
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
211
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
437-47
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Interaction of Hoechst 33258 with the minor groove of the A + T-rich DNA duplex d(GGTAATTACC)2 studied in solution by NMR spectroscopy.
pubmed:affiliation
School of Pharmaceutical Chemistry, Victorian College of Pharmacy, Parkville, Victoria, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't