Linked Life Data

8035432

Source:http://linkedlifedata.com/resource/pubmed/id/8035432

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
1994-8-18
pubmed:abstractText
Photoaffinity ligands are useful tools for the isolation, purification, and characterization of proteins. As a step toward the goal of producing a photoaffinity probe for the dopamine transporter, isocyanato and azido derivatives of 3-[(phenylcarbamoyl)oxy]ecgonine methyl ester were synthesized and tested for their ability to interact with the cocaine receptor of mammalian brain via two different assays. The ability of two isothiocyanato (N=C=S) (para and meta) and two azido (N3) (para and meta) derivatives, as well as (-)-cocaine, to inhibit [3H]cocaine binding and [3H]dopamine uptake and to covalently interact with the cocaine-binding site was tested. The p-N=C=S was the most potent, with IC50 values of 0.23 and 0.49 microM for [3H]cocaine binding and [3H]dopamine uptake. The m-N3 and p-N3 inhibited [3H]cocaine binding with IC50 values of 0.63 and 1.00 microM and inhibited [3H]dopamine uptake with IC50 values of 5.08 and 1.32 microM, respectively. Preincubation of synaptosomal membranes with the m- or p-N=C=S isomer either in reduced lighting or under ultraviolet light followed by two washes resulted in inhibition of 70% and 85% of [3H]cocaine binding, respectively, indicating the highly reactive properties of these compounds. After preincubation in reduced lighting, m-N3 and p-N3 inhibited 0% and 13% of [3H]cocaine binding, while following preincubation under ultraviolet light, the inhibition increased to 61% and 68%, respectively. Thus, the isothiocyanato derivatives appear to bind irreversibly to the cocaine receptor in the presence or absence of ultraviolet light, whereas the azido derivatives are photoreactive compounds which may prove useful in the purification of the receptor.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
8
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2249-52
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Synthesis of substituted 3-carbamoylecgonine methyl ester analogues: irreversible and photoaffinity ligands for the cocaine receptor/dopamine transporter.
pubmed:affiliation
Department of Pharmaceutical Science, University of Maryland, Baltimore 21201.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.