Potent inhibitors active against HIV reverse transcriptase with K101P, a mutation conferring rilpivirine resistance
- Autores
- Gray, William T.; Frey, Kathleen M.; Laskey, Sarah B.; Mislak, Andrea C.; Spasov, Krasimir A.; Lee, Won Gil; Bollini, Mariela; Siliciano, Robert F.; Jorgensen, William L.; Anderson, Karen S.
- Año de publicación
- 2015
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Catechol diether compounds have nanomolar antiviral and enzymatic activity against HIV with reverse transcriptase (RT) variants containing K101P, a mutation that confers high-level resistance to FDA-approved non-nucleoside inhibitors efavirenz and rilpivirine. Kinetic data suggests that RT (K101P) variants are as catalytically fit as wild-type and thus can potentially increase in the viral population as more antiviral regimens include efavirenz or rilpivirine. Comparison of wild-type structures and a new crystal structure of RT (K101P) in complex with a leading compound confirms that the K101P mutation is not a liability for the catechol diethers while suggesting that key interactions are lost with efavirenz and rilpivirine.
Fil: Gray, William T.. University of Yale; Estados Unidos
Fil: Frey, Kathleen M.. University of Yale; Estados Unidos
Fil: Laskey, Sarah B.. University Johns Hopkins; Estados Unidos
Fil: Mislak, Andrea C.. University of Yale; Estados Unidos
Fil: Spasov, Krasimir A.. University of Yale; Estados Unidos
Fil: Lee, Won Gil. University of Yale; Estados Unidos
Fil: Bollini, Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of Yale; Estados Unidos
Fil: Siliciano, Robert F.. University Johns Hopkins; Estados Unidos. Howard Hughes Medial Institute; Estados Unidos
Fil: Jorgensen, William L.. University of Yale; Estados Unidos
Fil: Anderson, Karen S.. University of Yale; Estados Unidos - Materia
-
HIV
Rreverse transcriptase
Non-nucleoside reverse transcriptase inhibitors
Resistance
Mutations - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/15923
Ver los metadatos del registro completo
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Potent inhibitors active against HIV reverse transcriptase with K101P, a mutation conferring rilpivirine resistanceGray, William T.Frey, Kathleen M.Laskey, Sarah B.Mislak, Andrea C.Spasov, Krasimir A.Lee, Won GilBollini, MarielaSiliciano, Robert F.Jorgensen, William L.Anderson, Karen S.HIVRreverse transcriptaseNon-nucleoside reverse transcriptase inhibitorsResistanceMutationshttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Catechol diether compounds have nanomolar antiviral and enzymatic activity against HIV with reverse transcriptase (RT) variants containing K101P, a mutation that confers high-level resistance to FDA-approved non-nucleoside inhibitors efavirenz and rilpivirine. Kinetic data suggests that RT (K101P) variants are as catalytically fit as wild-type and thus can potentially increase in the viral population as more antiviral regimens include efavirenz or rilpivirine. Comparison of wild-type structures and a new crystal structure of RT (K101P) in complex with a leading compound confirms that the K101P mutation is not a liability for the catechol diethers while suggesting that key interactions are lost with efavirenz and rilpivirine.Fil: Gray, William T.. University of Yale; Estados UnidosFil: Frey, Kathleen M.. University of Yale; Estados UnidosFil: Laskey, Sarah B.. University Johns Hopkins; Estados UnidosFil: Mislak, Andrea C.. University of Yale; Estados UnidosFil: Spasov, Krasimir A.. University of Yale; Estados UnidosFil: Lee, Won Gil. University of Yale; Estados UnidosFil: Bollini, Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of Yale; Estados UnidosFil: Siliciano, Robert F.. University Johns Hopkins; Estados Unidos. Howard Hughes Medial Institute; Estados UnidosFil: Jorgensen, William L.. University of Yale; Estados UnidosFil: Anderson, Karen S.. University of Yale; Estados UnidosAmerican Chemical Society2015-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/15923Gray, William T.; Frey, Kathleen M.; Laskey, Sarah B.; Mislak, Andrea C.; Spasov, Krasimir A.; et al.; Potent inhibitors active against HIV reverse transcriptase with K101P, a mutation conferring rilpivirine resistance; American Chemical Society; ACS Medicinal Chemistry Letters; 6; 10; 9-2015; 1075-10791948-5875enginfo:eu-repo/semantics/altIdentifier/doi/10.1021/acsmedchemlett.5b00254info:eu-repo/semantics/altIdentifier/url/http://pubs.acs.org/doi/10.1021/acsmedchemlett.5b00254info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4601059/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:04:36Zoai:ri.conicet.gov.ar:11336/15923instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:04:36.9CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Potent inhibitors active against HIV reverse transcriptase with K101P, a mutation conferring rilpivirine resistance |
title |
Potent inhibitors active against HIV reverse transcriptase with K101P, a mutation conferring rilpivirine resistance |
spellingShingle |
Potent inhibitors active against HIV reverse transcriptase with K101P, a mutation conferring rilpivirine resistance Gray, William T. HIV Rreverse transcriptase Non-nucleoside reverse transcriptase inhibitors Resistance Mutations |
title_short |
Potent inhibitors active against HIV reverse transcriptase with K101P, a mutation conferring rilpivirine resistance |
title_full |
Potent inhibitors active against HIV reverse transcriptase with K101P, a mutation conferring rilpivirine resistance |
title_fullStr |
Potent inhibitors active against HIV reverse transcriptase with K101P, a mutation conferring rilpivirine resistance |
title_full_unstemmed |
Potent inhibitors active against HIV reverse transcriptase with K101P, a mutation conferring rilpivirine resistance |
title_sort |
Potent inhibitors active against HIV reverse transcriptase with K101P, a mutation conferring rilpivirine resistance |
dc.creator.none.fl_str_mv |
Gray, William T. Frey, Kathleen M. Laskey, Sarah B. Mislak, Andrea C. Spasov, Krasimir A. Lee, Won Gil Bollini, Mariela Siliciano, Robert F. Jorgensen, William L. Anderson, Karen S. |
author |
Gray, William T. |
author_facet |
Gray, William T. Frey, Kathleen M. Laskey, Sarah B. Mislak, Andrea C. Spasov, Krasimir A. Lee, Won Gil Bollini, Mariela Siliciano, Robert F. Jorgensen, William L. Anderson, Karen S. |
author_role |
author |
author2 |
Frey, Kathleen M. Laskey, Sarah B. Mislak, Andrea C. Spasov, Krasimir A. Lee, Won Gil Bollini, Mariela Siliciano, Robert F. Jorgensen, William L. Anderson, Karen S. |
author2_role |
author author author author author author author author author |
dc.subject.none.fl_str_mv |
HIV Rreverse transcriptase Non-nucleoside reverse transcriptase inhibitors Resistance Mutations |
topic |
HIV Rreverse transcriptase Non-nucleoside reverse transcriptase inhibitors Resistance Mutations |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.4 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
Catechol diether compounds have nanomolar antiviral and enzymatic activity against HIV with reverse transcriptase (RT) variants containing K101P, a mutation that confers high-level resistance to FDA-approved non-nucleoside inhibitors efavirenz and rilpivirine. Kinetic data suggests that RT (K101P) variants are as catalytically fit as wild-type and thus can potentially increase in the viral population as more antiviral regimens include efavirenz or rilpivirine. Comparison of wild-type structures and a new crystal structure of RT (K101P) in complex with a leading compound confirms that the K101P mutation is not a liability for the catechol diethers while suggesting that key interactions are lost with efavirenz and rilpivirine. Fil: Gray, William T.. University of Yale; Estados Unidos Fil: Frey, Kathleen M.. University of Yale; Estados Unidos Fil: Laskey, Sarah B.. University Johns Hopkins; Estados Unidos Fil: Mislak, Andrea C.. University of Yale; Estados Unidos Fil: Spasov, Krasimir A.. University of Yale; Estados Unidos Fil: Lee, Won Gil. University of Yale; Estados Unidos Fil: Bollini, Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of Yale; Estados Unidos Fil: Siliciano, Robert F.. University Johns Hopkins; Estados Unidos. Howard Hughes Medial Institute; Estados Unidos Fil: Jorgensen, William L.. University of Yale; Estados Unidos Fil: Anderson, Karen S.. University of Yale; Estados Unidos |
description |
Catechol diether compounds have nanomolar antiviral and enzymatic activity against HIV with reverse transcriptase (RT) variants containing K101P, a mutation that confers high-level resistance to FDA-approved non-nucleoside inhibitors efavirenz and rilpivirine. Kinetic data suggests that RT (K101P) variants are as catalytically fit as wild-type and thus can potentially increase in the viral population as more antiviral regimens include efavirenz or rilpivirine. Comparison of wild-type structures and a new crystal structure of RT (K101P) in complex with a leading compound confirms that the K101P mutation is not a liability for the catechol diethers while suggesting that key interactions are lost with efavirenz and rilpivirine. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-09 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/15923 Gray, William T.; Frey, Kathleen M.; Laskey, Sarah B.; Mislak, Andrea C.; Spasov, Krasimir A.; et al.; Potent inhibitors active against HIV reverse transcriptase with K101P, a mutation conferring rilpivirine resistance; American Chemical Society; ACS Medicinal Chemistry Letters; 6; 10; 9-2015; 1075-1079 1948-5875 |
url |
http://hdl.handle.net/11336/15923 |
identifier_str_mv |
Gray, William T.; Frey, Kathleen M.; Laskey, Sarah B.; Mislak, Andrea C.; Spasov, Krasimir A.; et al.; Potent inhibitors active against HIV reverse transcriptase with K101P, a mutation conferring rilpivirine resistance; American Chemical Society; ACS Medicinal Chemistry Letters; 6; 10; 9-2015; 1075-1079 1948-5875 |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1021/acsmedchemlett.5b00254 info:eu-repo/semantics/altIdentifier/url/http://pubs.acs.org/doi/10.1021/acsmedchemlett.5b00254 info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4601059/ |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
American Chemical Society |
publisher.none.fl_str_mv |
American Chemical Society |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
reponame_str |
CONICET Digital (CONICET) |
collection |
CONICET Digital (CONICET) |
instname_str |
Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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1842269865249865728 |
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13.13397 |