Structural Studies and Structure Activity Relationships for Novel Computationally Designed Non-nucleoside Inhibitors and Their Interactions With HIV-1 Reverse Transcriptase
- Autores
- Frey, Kathleen M.; Bertoletti, Nicole; Chan, Albert H.; Ippolito, Joseph A.; Bollini, Mariela; Spasov, Krasimir A.; Jorgensen, William L.; Anderson, Karen S.
- Año de publicación
- 2022
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Reverse transcriptase (RT) from the human immunodeficiency virus continues to be an attractive drug target for antiretroviral therapy. June 2022 will commemorate the 30th anniversary of the first Human Immunodeficiency Virus (HIV) RT crystal structure complex that was solved with non-nucleoside reverse transcriptase inhibitor nevirapine. The release of this structure opened opportunities for designing many families of non-nucleoside reverse transcriptase inhibitors (NNRTIs). In paying tribute to the first RT-nevirapine structure, we have developed several compound classes targeting the non-nucleoside inhibitor binding pocket of HIV RT. Extensive analysis of crystal structures of RT in complex with the compounds informed iterations of structure-based drug design. Structures of seven additional complexes were determined and analyzed to summarize key interactions with residues in the non-nucleoside inhibitor binding pocket (NNIBP) of RT. Additional insights comparing structures with antiviral data and results from molecular dynamics simulations elucidate key interactions and dynamics between the nucleotide and non-nucleoside binding sites.
Fil: Frey, Kathleen M.. University of Yale; Estados Unidos
Fil: Bertoletti, Nicole. University of Yale; Estados Unidos
Fil: Chan, Albert H.. University of Yale; Estados Unidos
Fil: Ippolito, Joseph A.. University of Yale; Estados Unidos
Fil: Bollini, Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; Argentina. University of Yale; Estados Unidos
Fil: Spasov, Krasimir A.. University of Yale; Estados Unidos
Fil: Jorgensen, William L.. University of Yale; Estados Unidos
Fil: Anderson, Karen S.. University of Yale; Estados Unidos - Materia
-
COMPUTATIONAL CHEMISTRY
DRUG DESIGN
HIV RT
NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS
STRUCTURAL STUDIES - 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:11336/203785
Ver los metadatos del registro completo
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Structural Studies and Structure Activity Relationships for Novel Computationally Designed Non-nucleoside Inhibitors and Their Interactions With HIV-1 Reverse TranscriptaseFrey, Kathleen M.Bertoletti, NicoleChan, Albert H.Ippolito, Joseph A.Bollini, MarielaSpasov, Krasimir A.Jorgensen, William L.Anderson, Karen S.COMPUTATIONAL CHEMISTRYDRUG DESIGNHIV RTNON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORSSTRUCTURAL STUDIEShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Reverse transcriptase (RT) from the human immunodeficiency virus continues to be an attractive drug target for antiretroviral therapy. June 2022 will commemorate the 30th anniversary of the first Human Immunodeficiency Virus (HIV) RT crystal structure complex that was solved with non-nucleoside reverse transcriptase inhibitor nevirapine. The release of this structure opened opportunities for designing many families of non-nucleoside reverse transcriptase inhibitors (NNRTIs). In paying tribute to the first RT-nevirapine structure, we have developed several compound classes targeting the non-nucleoside inhibitor binding pocket of HIV RT. Extensive analysis of crystal structures of RT in complex with the compounds informed iterations of structure-based drug design. Structures of seven additional complexes were determined and analyzed to summarize key interactions with residues in the non-nucleoside inhibitor binding pocket (NNIBP) of RT. Additional insights comparing structures with antiviral data and results from molecular dynamics simulations elucidate key interactions and dynamics between the nucleotide and non-nucleoside binding sites.Fil: Frey, Kathleen M.. University of Yale; Estados UnidosFil: Bertoletti, Nicole. University of Yale; Estados UnidosFil: Chan, Albert H.. University of Yale; Estados UnidosFil: Ippolito, Joseph A.. University of Yale; Estados UnidosFil: Bollini, Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; Argentina. University of Yale; Estados UnidosFil: Spasov, Krasimir A.. University of Yale; Estados UnidosFil: Jorgensen, William L.. University of Yale; Estados UnidosFil: Anderson, Karen S.. University of Yale; Estados UnidosFrontiers Media2022-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/203785Frey, Kathleen M.; Bertoletti, Nicole; Chan, Albert H.; Ippolito, Joseph A.; Bollini, Mariela; et al.; Structural Studies and Structure Activity Relationships for Novel Computationally Designed Non-nucleoside Inhibitors and Their Interactions With HIV-1 Reverse Transcriptase; Frontiers Media; Frontiers in Molecular Biosciences; 9; 2-2022; 1-132296-889XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fmolb.2022.805187/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fmolb.2022.805187info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:51:46Zoai:ri.conicet.gov.ar:11336/203785instacron: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 09:51:46.698CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Structural Studies and Structure Activity Relationships for Novel Computationally Designed Non-nucleoside Inhibitors and Their Interactions With HIV-1 Reverse Transcriptase |
title |
Structural Studies and Structure Activity Relationships for Novel Computationally Designed Non-nucleoside Inhibitors and Their Interactions With HIV-1 Reverse Transcriptase |
spellingShingle |
Structural Studies and Structure Activity Relationships for Novel Computationally Designed Non-nucleoside Inhibitors and Their Interactions With HIV-1 Reverse Transcriptase Frey, Kathleen M. COMPUTATIONAL CHEMISTRY DRUG DESIGN HIV RT NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS STRUCTURAL STUDIES |
title_short |
Structural Studies and Structure Activity Relationships for Novel Computationally Designed Non-nucleoside Inhibitors and Their Interactions With HIV-1 Reverse Transcriptase |
title_full |
Structural Studies and Structure Activity Relationships for Novel Computationally Designed Non-nucleoside Inhibitors and Their Interactions With HIV-1 Reverse Transcriptase |
title_fullStr |
Structural Studies and Structure Activity Relationships for Novel Computationally Designed Non-nucleoside Inhibitors and Their Interactions With HIV-1 Reverse Transcriptase |
title_full_unstemmed |
Structural Studies and Structure Activity Relationships for Novel Computationally Designed Non-nucleoside Inhibitors and Their Interactions With HIV-1 Reverse Transcriptase |
title_sort |
Structural Studies and Structure Activity Relationships for Novel Computationally Designed Non-nucleoside Inhibitors and Their Interactions With HIV-1 Reverse Transcriptase |
dc.creator.none.fl_str_mv |
Frey, Kathleen M. Bertoletti, Nicole Chan, Albert H. Ippolito, Joseph A. Bollini, Mariela Spasov, Krasimir A. Jorgensen, William L. Anderson, Karen S. |
author |
Frey, Kathleen M. |
author_facet |
Frey, Kathleen M. Bertoletti, Nicole Chan, Albert H. Ippolito, Joseph A. Bollini, Mariela Spasov, Krasimir A. Jorgensen, William L. Anderson, Karen S. |
author_role |
author |
author2 |
Bertoletti, Nicole Chan, Albert H. Ippolito, Joseph A. Bollini, Mariela Spasov, Krasimir A. Jorgensen, William L. Anderson, Karen S. |
author2_role |
author author author author author author author |
dc.subject.none.fl_str_mv |
COMPUTATIONAL CHEMISTRY DRUG DESIGN HIV RT NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS STRUCTURAL STUDIES |
topic |
COMPUTATIONAL CHEMISTRY DRUG DESIGN HIV RT NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS STRUCTURAL STUDIES |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
Reverse transcriptase (RT) from the human immunodeficiency virus continues to be an attractive drug target for antiretroviral therapy. June 2022 will commemorate the 30th anniversary of the first Human Immunodeficiency Virus (HIV) RT crystal structure complex that was solved with non-nucleoside reverse transcriptase inhibitor nevirapine. The release of this structure opened opportunities for designing many families of non-nucleoside reverse transcriptase inhibitors (NNRTIs). In paying tribute to the first RT-nevirapine structure, we have developed several compound classes targeting the non-nucleoside inhibitor binding pocket of HIV RT. Extensive analysis of crystal structures of RT in complex with the compounds informed iterations of structure-based drug design. Structures of seven additional complexes were determined and analyzed to summarize key interactions with residues in the non-nucleoside inhibitor binding pocket (NNIBP) of RT. Additional insights comparing structures with antiviral data and results from molecular dynamics simulations elucidate key interactions and dynamics between the nucleotide and non-nucleoside binding sites. Fil: Frey, Kathleen M.. University of Yale; Estados Unidos Fil: Bertoletti, Nicole. University of Yale; Estados Unidos Fil: Chan, Albert H.. University of Yale; Estados Unidos Fil: Ippolito, Joseph A.. University of Yale; Estados Unidos Fil: Bollini, Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; Argentina. University of Yale; Estados Unidos Fil: Spasov, Krasimir A.. University of Yale; Estados Unidos Fil: Jorgensen, William L.. University of Yale; Estados Unidos Fil: Anderson, Karen S.. University of Yale; Estados Unidos |
description |
Reverse transcriptase (RT) from the human immunodeficiency virus continues to be an attractive drug target for antiretroviral therapy. June 2022 will commemorate the 30th anniversary of the first Human Immunodeficiency Virus (HIV) RT crystal structure complex that was solved with non-nucleoside reverse transcriptase inhibitor nevirapine. The release of this structure opened opportunities for designing many families of non-nucleoside reverse transcriptase inhibitors (NNRTIs). In paying tribute to the first RT-nevirapine structure, we have developed several compound classes targeting the non-nucleoside inhibitor binding pocket of HIV RT. Extensive analysis of crystal structures of RT in complex with the compounds informed iterations of structure-based drug design. Structures of seven additional complexes were determined and analyzed to summarize key interactions with residues in the non-nucleoside inhibitor binding pocket (NNIBP) of RT. Additional insights comparing structures with antiviral data and results from molecular dynamics simulations elucidate key interactions and dynamics between the nucleotide and non-nucleoside binding sites. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-02 |
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/11336/203785 Frey, Kathleen M.; Bertoletti, Nicole; Chan, Albert H.; Ippolito, Joseph A.; Bollini, Mariela; et al.; Structural Studies and Structure Activity Relationships for Novel Computationally Designed Non-nucleoside Inhibitors and Their Interactions With HIV-1 Reverse Transcriptase; Frontiers Media; Frontiers in Molecular Biosciences; 9; 2-2022; 1-13 2296-889X CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/203785 |
identifier_str_mv |
Frey, Kathleen M.; Bertoletti, Nicole; Chan, Albert H.; Ippolito, Joseph A.; Bollini, Mariela; et al.; Structural Studies and Structure Activity Relationships for Novel Computationally Designed Non-nucleoside Inhibitors and Their Interactions With HIV-1 Reverse Transcriptase; Frontiers Media; Frontiers in Molecular Biosciences; 9; 2-2022; 1-13 2296-889X CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fmolb.2022.805187/full info:eu-repo/semantics/altIdentifier/doi/10.3389/fmolb.2022.805187 |
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 |
Frontiers Media |
publisher.none.fl_str_mv |
Frontiers Media |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
reponame_str |
CONICET Digital (CONICET) |
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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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1842269116243640320 |
score |
13.13397 |