Linked Life Data

21273081

Source:http://linkedlifedata.com/resource/pubmed/id/21273081

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2011-2-14
pubmed:abstractText
Herein we demonstrate that competition between candidate kinetic stabilizer binding to transthyretin (TTR) and stilbene binding to and reaction with the same thyroxine sites within TTR can be utilized to discover potent and highly selective non-covalent TTR amyloidogenesis inhibitors. We report two stilbenes, S1 and S2, for use in distinct competition assays. Each bind selectively to TTR and then chemoselectively react to form an amide bond with the Lys-15 residue of TTR, creating a fluorescent conjugate. We used 28 TTR kinetic stabilizers exhibiting a known spectrum of plasma TTR binding selectivities and TTR amyloid fibril inhibition efficacies to validate the 'TTR fluorescence conjugate competition assay'. The kinetic stabilizers competed with S1 for binding to recombinant TTR in buffer and with S2 for binding to endogenous levels of TTR in human blood serum. In both assay scenarios, we demonstrate that the lower the TTR-stilbene conjugate fluorescence after a 3 h competition, the greater the binding selectivity and potency of the candidate TTR kinetic stabilizer. These assays, particularly the assay utilizing S2 in human serum, replace two assays previously utilized to gather the same information. While not the focus of this manuscript, it is clear that the 'TTR fluorescence conjugate competition assay' could be adapted for high throughput screening applications.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1464-3391
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1505-14
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
A competition assay to identify amyloidogenesis inhibitors by monitoring the fluorescence emitted by the covalent attachment of a stilbene derivative to transthyretin.
pubmed:affiliation
Department of New Drug Discovery and Development, Chungnam National University, Daejon 305-764, Republic of Korea.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural