Seeking novel leads through structure-based pharmacophore design
Autor(a) principal: | |
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Data de Publicação: | 2002 |
Outros Autores: | |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Journal of the Brazilian Chemical Society (Online) |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532002000600008 |
Resumo: | We developed a procedure that identifies "novel" biologically active compounds that are expected to be distinct from known active compounds with respect to specificity and other such characteristics. The procedure involves mapping a set of known active compounds (training set) onto all possible hydrogen bonding and lipophilic interaction sites of an enzyme active site and flagging those interactions that are utilized by the training set. These flagged sites are removed (except for those that are deemed critical binding sites), leaving only potential interaction sites not utilized by the active compounds. Once unflagged sites were enumerated, pharmacophore models were then generated, scored, and prioritized where the top pharmacophore model was used to search 3D databases for identifying new leads. This procedure was applied to HIV-1 protease inhibitors. Several compounds retrieved by the top pharmacophore model were identified as moderately active (in mMolar range). |
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Journal of the Brazilian Chemical Society (Online) |
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Seeking novel leads through structure-based pharmacophore designpharmacophoresstructure-based design3D databsesWe developed a procedure that identifies "novel" biologically active compounds that are expected to be distinct from known active compounds with respect to specificity and other such characteristics. The procedure involves mapping a set of known active compounds (training set) onto all possible hydrogen bonding and lipophilic interaction sites of an enzyme active site and flagging those interactions that are utilized by the training set. These flagged sites are removed (except for those that are deemed critical binding sites), leaving only potential interaction sites not utilized by the active compounds. Once unflagged sites were enumerated, pharmacophore models were then generated, scored, and prioritized where the top pharmacophore model was used to search 3D databases for identifying new leads. This procedure was applied to HIV-1 protease inhibitors. Several compounds retrieved by the top pharmacophore model were identified as moderately active (in mMolar range).Sociedade Brasileira de Química2002-11-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532002000600008Journal of the Brazilian Chemical Society v.13 n.6 2002reponame:Journal of the Brazilian Chemical Society (Online)instname:Sociedade Brasileira de Química (SBQ)instacron:SBQ10.1590/S0103-50532002000600008info:eu-repo/semantics/openAccessFisher,Luke S.Güner,Osman F.eng2015-11-26T00:00:00Zoai:scielo:S0103-50532002000600008Revistahttp://jbcs.sbq.org.brONGhttps://old.scielo.br/oai/scielo-oai.php||office@jbcs.sbq.org.br1678-47900103-5053opendoar:2015-11-26T00:00Journal of the Brazilian Chemical Society (Online) - Sociedade Brasileira de Química (SBQ)false |
dc.title.none.fl_str_mv |
Seeking novel leads through structure-based pharmacophore design |
title |
Seeking novel leads through structure-based pharmacophore design |
spellingShingle |
Seeking novel leads through structure-based pharmacophore design Fisher,Luke S. pharmacophores structure-based design 3D databses |
title_short |
Seeking novel leads through structure-based pharmacophore design |
title_full |
Seeking novel leads through structure-based pharmacophore design |
title_fullStr |
Seeking novel leads through structure-based pharmacophore design |
title_full_unstemmed |
Seeking novel leads through structure-based pharmacophore design |
title_sort |
Seeking novel leads through structure-based pharmacophore design |
author |
Fisher,Luke S. |
author_facet |
Fisher,Luke S. Güner,Osman F. |
author_role |
author |
author2 |
Güner,Osman F. |
author2_role |
author |
dc.contributor.author.fl_str_mv |
Fisher,Luke S. Güner,Osman F. |
dc.subject.por.fl_str_mv |
pharmacophores structure-based design 3D databses |
topic |
pharmacophores structure-based design 3D databses |
description |
We developed a procedure that identifies "novel" biologically active compounds that are expected to be distinct from known active compounds with respect to specificity and other such characteristics. The procedure involves mapping a set of known active compounds (training set) onto all possible hydrogen bonding and lipophilic interaction sites of an enzyme active site and flagging those interactions that are utilized by the training set. These flagged sites are removed (except for those that are deemed critical binding sites), leaving only potential interaction sites not utilized by the active compounds. Once unflagged sites were enumerated, pharmacophore models were then generated, scored, and prioritized where the top pharmacophore model was used to search 3D databases for identifying new leads. This procedure was applied to HIV-1 protease inhibitors. Several compounds retrieved by the top pharmacophore model were identified as moderately active (in mMolar range). |
publishDate |
2002 |
dc.date.none.fl_str_mv |
2002-11-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532002000600008 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532002000600008 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1590/S0103-50532002000600008 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Sociedade Brasileira de Química |
publisher.none.fl_str_mv |
Sociedade Brasileira de Química |
dc.source.none.fl_str_mv |
Journal of the Brazilian Chemical Society v.13 n.6 2002 reponame:Journal of the Brazilian Chemical Society (Online) instname:Sociedade Brasileira de Química (SBQ) instacron:SBQ |
instname_str |
Sociedade Brasileira de Química (SBQ) |
instacron_str |
SBQ |
institution |
SBQ |
reponame_str |
Journal of the Brazilian Chemical Society (Online) |
collection |
Journal of the Brazilian Chemical Society (Online) |
repository.name.fl_str_mv |
Journal of the Brazilian Chemical Society (Online) - Sociedade Brasileira de Química (SBQ) |
repository.mail.fl_str_mv |
||office@jbcs.sbq.org.br |
_version_ |
1750318164968734720 |