Linked Life Data

16942015

Source:http://linkedlifedata.com/resource/pubmed/id/16942015

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
2006-8-31
pubmed:abstractText
Philanthotoxins are uncompetitive antagonists of Ca2+-permeable AMPA receptors presumed to bind to the pore-forming region, but a detailed molecular mechanism for this interaction is missing. Here a small library of novel philanthotoxins was designed and synthesized using a solid-phase strategy. The biological activities were investigated at cloned and "native" AMPA receptors using electrophysiological techniques. A distinct relationship between length of the polyamine moiety and the location of a secondary amino group was observed. Fitting the data to the Woodhull equation allowed the first experimental demonstration of the relative location and orientation of the philanthotoxin molecule in the receptor. These results were corroborated by in silico studies using a homology model of the AMPA receptor ion channel. Together these studies provide strong evidence for a molecular mechanism by which polyamine toxins antagonize the AMPA receptor ion channel and provide the basis for rational development of uncompetitive antagonists of AMPA receptors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
7
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5414-23
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Uncompetitive antagonism of AMPA receptors: Mechanistic insights from studies of polyamine toxin derivatives.
pubmed:affiliation
Department of Medicinal Chemistry, The Danish University of Pharmaceutical Sciences, DK-2100 Copenhagen, Denmark.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't