Linked Life Data

17481659

Source:http://linkedlifedata.com/resource/pubmed/id/17481659

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-5-21
pubmed:abstractText
Binding of nucleic acids to the prion protein (PrP) created a conundrum that required distinguishing between non-specific interactions and biologically important polynucleotides. In the process of developing selective ligands for PrP, we found using a single-stranded DNA thioaptamer library that the binding of thioaptamers to PrP occurs on at least two different sites on the protein. Selection against recombinant (rec) PrP of Syrian hamster (SHa) sequence 90-231 folded into an alpha-helical-rich conformation identified a 12-base consensus sequence within a series of 20 thioaptamers, all of which consist of 40 bases. Each thioaptamer was comprised of both normal and thio-dA modified bases. One thioaptamer designated 97 bound to recSHaPrP with affinity of 0.58(+/-0.1) nM; lower affinities for bovine (Bo), and human (Hu) were found, establishing that binding is dependent on the primary structure of PrP. High affinity binding of thioaptamer 97 to PrP was found to be mediated through the dodecyl sequence GACACAAGCCGA within the consensus region with five critical backbone modifications 5' to each dA residue. A control oligonucleotide with an equivalent number of phosphorothioates to thioaptamer 97 and a scrambled consensus sequence could not distinguish among the three PrP sequences. Control oligonucleotides bearing non-selected sequences bound to PrP at a sequence-independent DNA-binding site. In contrast, the high-affinity binding of thioaptamer 97 to PrP depends on (1) backbone modifications, (2) oligonucleotide sequence, and (3) PrP sequence.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-2836
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
369
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1001-14
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Thioaptamer interactions with prion proteins: sequence-specific and non-specific binding sites.
pubmed:affiliation
Institute for Neurodegenerative Diseases, University of California San Francisco, CA 94143-0518, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural