Linked Life Data

21669531

Source:http://linkedlifedata.com/resource/pubmed/id/21669531

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2011-7-1
pubmed:abstractText
Evidence was acquired prior to suggest that the vesicular glutamate transporter (VGLUT) but not other glutamate transporters were inhibited by structures containing a weakly basic ?-amino group. To test this hypothesis, a series of analogs using a hydantoin (pK(a)?9.1) isostere were synthesized and analyzed as inhibitors of VGLUT and the obligate cystine-glutamate transporter (system x(c)(-)). Of the hydantoin analogs tested, a thiophene-5-carboxaldehyde analog 2l and a bis-hydantoin 4b were relatively strong inhibitors of VGLUT reducing uptake to less than 6% of control at 5mM but few inhibited system x(c)(-) greater than 50% of control. The benzene-2,4-disulfonic acid analog 2b and p-diaminobenzene analog 2e were also good hydantoin-based inhibitors of VGLUT reducing uptake by 11% and 23% of control, respectively, but neither analog was effective as a system x(c)(-) inhibitor. In sum, a hydantoin isostere adds the requisite chemical properties needed to produce selective inhibitors of VGLUT.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1464-3405
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4358-62
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Use of the hydantoin isostere to produce inhibitors showing selectivity toward the vesicular glutamate transporter versus the obligate exchange transporter system x(c)(-).
pubmed:affiliation
Core Laboratory for Neuromolecular Production, Department of Biomedical and Pharmaceutical Sciences, The University of Montana, Missoula, MT 59812, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural