Linked Life Data

8286393

Source:http://linkedlifedata.com/resource/pubmed/id/8286393

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1994-2-18
pubmed:abstractText
The binding to DNA by calicheamicin epsilon (CLM epsilon), the rearranged and reduced product of the diynene antitumor antibiotic calicheamicin gamma 1I (CLM gamma 1I), was studied using the method of hydroxyl radical footprinting. The drug binding sites determined in this way were compared to locations of double-stranded DNA cleavage by thiol-activated CLM gamma 1I. The results of these experiments show that CLM epsilon lies in the minor groove in an extended conformation protecting approximately four nucleotides on each strand of DNA. Sites of CLM epsilon binding correlate to sites of CLM gamma 1I cleavage with protection by CLM epsilon occurring mainly to the 3' side of the site of C5' hydrogen abstraction. From these results, it is possible to propose global structures of the drug/DNA complexes such that the oligosaccharide side chain is arrayed to the 3' side of the site of C5' hydrogen abstraction. This conclusion is entirely consistent with the results of recent atom-transfer experiments [Hangeland, J.J., De Voss, J.J., Heath, J.A., Townsend, C.A., Ding, W.-D., Ashcroft, J., & Ellestad, G.A. (1992) J. Am. Chem. Soc. 114, 9200-9202]. Somewhat greater protection on the strand undergoing C5' hydrogen abstraction was observed to the 5' side of the site of attack owing presumably to proximity of the methyl carbamate portion of the drug with DNA. Overall, binding is seen where cleavage is seen in accord with thermodynamics of drug association to DNA being important in determining the sites of cleavage.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
614-21
pubmed:dateRevised
2008-8-29
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Hydroxyl radical footprinting of calicheamicin. Relationship of DNA binding to cleavage.
pubmed:affiliation
Department of Chemistry, Johns Hopkins University, Baltimore, Maryland 21218.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't