Linked Life Data

8204221

Source:http://linkedlifedata.com/resource/pubmed/id/8204221

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1994-7-14
pubmed:abstractText
The interaction between DNA and two peptide-acridine conjugates containing one (1) or two (2) moieties of the Ser-Pro-Lys-Lys (SPKK) minor groove-binding peptide motif has been studied by a combination of hydrodynamic, biochemical and spectroscopic methods including diffusion-enhanced luminescence energy transfer (DELET) measurements with a Tb(III) lanthanide chelate as donor. Viscometric titrations do not reveal any significant difference between the two hybrid molecules which both unwind (by about 15 degrees) and extend the DNA similarly. DELET measurements show that the acridinyl chromophore of compounds 1 and 2 is much more accessible than that of a simple monointercalating drug such as acridine orange or ethidium. The accessibility factor increases proportionally with the peptide length, reflecting the extent of perturbation imposed upon the intercalating chromophore by the binding to DNA of the peptide moiety of the hybrids. Experiments with the osmium tetroxide-bispyridine reagent indicate that the two hybrid compounds both affect the local conformation of DNA rendering certain thymine residues conspicuously accessible to the probe. The drug-induced sites of hyperreactivity towards OsO4 in DNA are very similar with the exception of a short run of three T residues which is attacked more strongly in the presence of tetrapeptide-acridine conjugate 1 than with the octapeptide-acridine conjugate 2. These results are fully in agreement with previous footprinting studies and support the view that a minimum of two SPKK motifs is required to mimic the AT-specific minor groove binding antibiotic netropsin. On the basis of the DNA-binding properties of these two peptide-acridine hybrids, we present DNA-binding models in which the acridinyl moiety of compound 1 protrudes slightly outside the double helix but remains more or less parallel to the plane of the base-pairs. In contrast, with compound 2, where the octapeptide SPKKSPKK is bound to the minor groove, we postulate that the chromophore lies only partially overlapped with the base pairs in the intercalation site and, in addition, the heterocyclic chromophore is significantly tilted with respect to the double helix axis. Electric linear dichroism and DELET measurements with chromatin reveal that the presence of histone proteins affects the intercalative binding of compound 2 while it has practically no effect on the binding of compound 1.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0739-1102
pubmed:author
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
881-900
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Interaction of two peptide-acridine conjugates containing the SPKK peptide motif with DNA and chromatin.
pubmed:affiliation
Laboratoire de Chimie Macromoléculaire et Chimie Physique, Université de Liège, Belgium.
pubmed:publicationType
Journal Article, Comparative Study