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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2008-2-8
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pubmed:abstractText |
A population of 100 graphics models of the human 5-HT6 serotonin receptor was constructed based on the structure of bovine rhodopsin. The endogenous tryptamine-based agonist serotonin (5-HT; 1) and the benzenesulfonyl-containing tryptamine-derived 5-HT6 receptor antagonist MS-245 (4a) were automatically docked with each of the 100 receptor models using a genetic algorithm approach. Similar studies were conducted with the more selective 5-HT6 receptor agonist EMDT (5) and optical isomers of EMDT-related analog 8, as well as with optical isomers of MS-245 (4a)-related and benzenesulfonyl-containing pyrrolidine 6 and aminotetralin 7. Although associated with the same general aromatic/hydrophobic binding cluster, 5-HT (1) and MS-245 (4a) were found to preferentially bind with distinct receptor conformations, and did so with different binding orientations (i.e., poses). A 5-HT pose/model was found to be common to EMDT (5) and its analogs, whereas that identified for MS-245 (4a) was found common to benzenesulfonyl-containing compounds. Specific amino acid residues were identified that can participate in binding, and evaluation of a sulfenamide analog of MS-245 indicates for the first time that the presence of the sulfonyl oxygen atoms enhances receptor affinity. The results indicate that the presence or absence of an N1-benzenesulfonyl group is a major determinant of the manner in which tryptamine-related agents bind at 5-HT6 serotonin receptors.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Benzenesulfonates,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/N1-benzenesulfonyl-5-methoxy-N,N-dim...,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrrolidines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Rhodopsin,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Receptor Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Tetrahydronaphthalenes,
http://linkedlifedata.com/resource/pubmed/chemical/Tryptamines,
http://linkedlifedata.com/resource/pubmed/chemical/serotonin 6 receptor
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0022-2623
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
14
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pubmed:volume |
51
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
603-11
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:18201064-Algorithms,
pubmed-meshheading:18201064-Animals,
pubmed-meshheading:18201064-Benzenesulfonates,
pubmed-meshheading:18201064-Cattle,
pubmed-meshheading:18201064-Humans,
pubmed-meshheading:18201064-Hydrophobic and Hydrophilic Interactions,
pubmed-meshheading:18201064-Ligands,
pubmed-meshheading:18201064-Models, Molecular,
pubmed-meshheading:18201064-Mutagenesis, Site-Directed,
pubmed-meshheading:18201064-Protein Conformation,
pubmed-meshheading:18201064-Pyrrolidines,
pubmed-meshheading:18201064-Receptors, Serotonin,
pubmed-meshheading:18201064-Rhodopsin,
pubmed-meshheading:18201064-Serotonin,
pubmed-meshheading:18201064-Serotonin Antagonists,
pubmed-meshheading:18201064-Serotonin Receptor Agonists,
pubmed-meshheading:18201064-Stereoisomerism,
pubmed-meshheading:18201064-Structure-Activity Relationship,
pubmed-meshheading:18201064-Tetrahydronaphthalenes,
pubmed-meshheading:18201064-Tryptamines
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pubmed:year |
2008
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pubmed:articleTitle |
Binding of serotonin and N1-benzenesulfonyltryptamine-related analogs at human 5-HT6 serotonin receptors: receptor modeling studies.
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pubmed:affiliation |
Department of Medicinal Chemistry, School of Pharmacy, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298-0540, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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