Linked Life Data

6101079

Source:http://linkedlifedata.com/resource/pubmed/id/6101079

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1990-3-14
pubmed:abstractText
Antibiotic netropsin is known to bind specifically to A and T regions in DNA; the mode of binding being non-intercalative. Obviously, H-bonding between the proton donors of netropsin and acceptors N3 of A and O2 of T comes as a strong possibility which might render this specificity. In netropsin there could be 8 proton donors: four terminal amino groups and four internal imino groups. However, methylation of the terminal amino groups does not alter the binding affinity of netropsin to DNA--but the modification of the internal imino groups significantly lowers the binding affinity. Hence, the logical conclusion is that netropsin may specifically interact with A and T through H-bonding and in order to do so, it should approach the helix from the minor groove. The present paper provides experimental data which verify the conclusion mentioned above. Using poly(dA-dT).poly(dA-dT) as a model system it was observed following a thorough theoretical stereochemical analysis that netropsin could bind to -(T-A-T) sequence of the polymer in the B-form through the minor groove by forming specific H-bonding. Models could be either right or left-handed B-DNA with a mono or dinucleotide repeat. By monitoring the 31P signals of free poly(dA-dT).poly(dA-dT) and netropsin-poly(dA-dT).poly(dA-dT) complex we show that the drug changes the DNA structure from essentially a mononucleotide repeat to that of very dominant dinucleotide repeat; however the base-pairing in the DNA-drug complex remain to be Watson-Crick. Whether H-bonding is the specific mode of interaction was judged by monitoring the imino protons of netropsin in the presence of poly(dA-dT).poly(dA-dT). This experiment was conducted in 90% H2O + 10% D2O using the time-shared long pulse. It was found that exchangeable imino protons of netropsin appear in the drug-DNA complex and disappear upon increasing the D2O content; thus confirming that H-bonding is indeed the specific mode of interaction. From these and several NOE measurements, we propose a structure for poly(dA-dT).poly(dA-dT)-netropsin complex. In summary, experimental data indicate that netropsin binds to poly(dA-dT).poly(dA-dT) by forming specific hydrogen bonds and that the binding interaction causes the structure to adopt a Watson-Crick paired dinucleotide repeat motif.(ABSTRACT TRUNCATED AT 400 WORDS)
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0739-1102
pubmed:author
pubmed:issnType
Print
pubmed:volume
1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1457-72
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1984
pubmed:articleTitle
Structure and dynamics of netropsin-poly(dA-dT).poly(dA-dT) complex: 500 MHz 1H NMR studies.
pubmed:affiliation
Institute of Biomolecular Stereodynamics, State University of New York, Albany 12222.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.