A platform for designing HIV integrase inhibitors. Part 2: A two-metal binding model as a potential mechanism of HIV integrase inhibitors
For advanced understanding of mechanism of chelating inhibitors. We propose a two-metal binding model as a potential mechanism of chelating inhibitors against HIV integrase (HIV IN) represented by 2-hydroxy-3-heteroaryl acrylic acids (HHAAs). Potential inhibitors would bind to two metal ions in the...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry 2006-12, Vol.14 (24), p.8420-8429 |
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| container_issue | 24 |
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| container_title | Bioorganic & medicinal chemistry |
| container_volume | 14 |
| creator | Kawasuji, Takashi Fuji, Masahiro Yoshinaga, Tomokazu Sato, Akihiko Fujiwara, Tamio Kiyama, Ryuichi |
| description | For advanced understanding of mechanism of chelating inhibitors.
We propose a two-metal binding model as a potential mechanism of chelating inhibitors against HIV integrase (HIV IN) represented by 2-hydroxy-3-heteroaryl acrylic acids (HHAAs). Potential inhibitors would bind to two metal ions in the active site of HIV IN to prevent human DNA from undergoing the integration reaction. Correlation of the results of metal (Mg
2+ and Mn
2+) titration studies with HIV IN inhibition for a series of active and inactive compounds provides support for the model. Results suggest Mg
2+ is an essential cofactor for chelating inhibitors. |
| doi_str_mv | 10.1016/j.bmc.2006.08.043 |
| format | Article |
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We propose a two-metal binding model as a potential mechanism of chelating inhibitors against HIV integrase (HIV IN) represented by 2-hydroxy-3-heteroaryl acrylic acids (HHAAs). Potential inhibitors would bind to two metal ions in the active site of HIV IN to prevent human DNA from undergoing the integration reaction. Correlation of the results of metal (Mg
2+ and Mn
2+) titration studies with HIV IN inhibition for a series of active and inactive compounds provides support for the model. Results suggest Mg
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We propose a two-metal binding model as a potential mechanism of chelating inhibitors against HIV integrase (HIV IN) represented by 2-hydroxy-3-heteroaryl acrylic acids (HHAAs). Potential inhibitors would bind to two metal ions in the active site of HIV IN to prevent human DNA from undergoing the integration reaction. Correlation of the results of metal (Mg
2+ and Mn
2+) titration studies with HIV IN inhibition for a series of active and inactive compounds provides support for the model. Results suggest Mg
2+ is an essential cofactor for chelating inhibitors.</description><subject>Acrylates - chemical synthesis</subject><subject>Acrylates - chemistry</subject><subject>Acrylates - pharmacology</subject><subject>Anti-HIV Agents - chemical synthesis</subject><subject>Anti-HIV Agents - chemistry</subject><subject>Anti-HIV Agents - pharmacology</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antiviral agents</subject><subject>Binding Sites</subject><subject>Biological and medical sciences</subject><subject>Chelating Agents - chemical synthesis</subject><subject>Chelating Agents - chemistry</subject><subject>Chelating Agents - pharmacology</subject><subject>Docking model</subject><subject>Drug Design</subject><subject>HIV Integrase - chemistry</subject><subject>HIV Integrase - metabolism</subject><subject>HIV integrase inhibitor</subject><subject>HIV Integrase Inhibitors - chemical synthesis</subject><subject>HIV Integrase Inhibitors - chemistry</subject><subject>HIV Integrase Inhibitors - pharmacology</subject><subject>HIV-1 - drug effects</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Inhibition mechanism</subject><subject>Magnesium - metabolism</subject><subject>Manganese - metabolism</subject><subject>Medical sciences</subject><subject>Metal affinity</subject><subject>Models, Biological</subject><subject>Models, Molecular</subject><subject>Molecular Structure</subject><subject>Pharmacology. Drug treatments</subject><subject>Structure-Activity Relationship</subject><subject>Two-metal binding model</subject><issn>0968-0896</issn><issn>1464-3391</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctu1DAUhi1ERYfCA7BB3sAuwXYSX2A1qoBWqtQuClvLl5OpR0k82B4qHoG3xqMZqStg42PpfP8vyx9CbyhpKaH8w7a1s2sZIbwlsiV99wytaM_7pusUfY5WRHHZEKn4OXqZ85YQwnpFX6BzKggZeiJW6Pca7yZTxphmXA_sIYfNEpYNvrr-jsNSYJNMhnp7CDaUmHKL70wqmH3Ea1weYzNDMRO2YfGH1Bw9TNhkbPAuFlhKqMsZ3INZQp5xHP_a-wqdjWbK8Po0L9C3L5_vL6-am9uv15frm8b1lJUGJJVMcuYVZ6O0wlpvu8FxJwYvGIhRKnBMSCKsorwD40Xv_Dj0YNioLHQX6P2xd5fijz3koueQHUyTWSDus-aSUlXL_wsywgQVqqsgPYIuxZwTjHqXwmzSL02JPojSW11F6YMoTaSuomrm7al8b2fwT4mTmQq8OwEmOzONySwu5CdOMsE4GSr36chB_bOfAZLOLsDiwIcErmgfwz-e8QfSurFL</recordid><startdate>20061215</startdate><enddate>20061215</enddate><creator>Kawasuji, Takashi</creator><creator>Fuji, Masahiro</creator><creator>Yoshinaga, Tomokazu</creator><creator>Sato, Akihiko</creator><creator>Fujiwara, Tamio</creator><creator>Kiyama, Ryuichi</creator><general>Elsevier Ltd</general><general>Elsevier Science</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7T7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20061215</creationdate><title>A platform for designing HIV integrase inhibitors. Part 2: A two-metal binding model as a potential mechanism of HIV integrase inhibitors</title><author>Kawasuji, Takashi ; Fuji, Masahiro ; Yoshinaga, Tomokazu ; Sato, Akihiko ; Fujiwara, Tamio ; Kiyama, Ryuichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-e8182862d962f8b7bbdb35c6c75d72e7f89ec27807b9163ead74cdf54ea2f9be3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Acrylates - chemical synthesis</topic><topic>Acrylates - chemistry</topic><topic>Acrylates - pharmacology</topic><topic>Anti-HIV Agents - chemical synthesis</topic><topic>Anti-HIV Agents - chemistry</topic><topic>Anti-HIV Agents - pharmacology</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antiviral agents</topic><topic>Binding Sites</topic><topic>Biological and medical sciences</topic><topic>Chelating Agents - chemical synthesis</topic><topic>Chelating Agents - chemistry</topic><topic>Chelating Agents - pharmacology</topic><topic>Docking model</topic><topic>Drug Design</topic><topic>HIV Integrase - chemistry</topic><topic>HIV Integrase - metabolism</topic><topic>HIV integrase inhibitor</topic><topic>HIV Integrase Inhibitors - chemical synthesis</topic><topic>HIV Integrase Inhibitors - chemistry</topic><topic>HIV Integrase Inhibitors - pharmacology</topic><topic>HIV-1 - drug effects</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Inhibition mechanism</topic><topic>Magnesium - metabolism</topic><topic>Manganese - metabolism</topic><topic>Medical sciences</topic><topic>Metal affinity</topic><topic>Models, Biological</topic><topic>Models, Molecular</topic><topic>Molecular Structure</topic><topic>Pharmacology. Drug treatments</topic><topic>Structure-Activity Relationship</topic><topic>Two-metal binding model</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kawasuji, Takashi</creatorcontrib><creatorcontrib>Fuji, Masahiro</creatorcontrib><creatorcontrib>Yoshinaga, Tomokazu</creatorcontrib><creatorcontrib>Sato, Akihiko</creatorcontrib><creatorcontrib>Fujiwara, Tamio</creatorcontrib><creatorcontrib>Kiyama, Ryuichi</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Bioorganic & medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kawasuji, Takashi</au><au>Fuji, Masahiro</au><au>Yoshinaga, Tomokazu</au><au>Sato, Akihiko</au><au>Fujiwara, Tamio</au><au>Kiyama, Ryuichi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A platform for designing HIV integrase inhibitors. Part 2: A two-metal binding model as a potential mechanism of HIV integrase inhibitors</atitle><jtitle>Bioorganic & medicinal chemistry</jtitle><addtitle>Bioorg Med Chem</addtitle><date>2006-12-15</date><risdate>2006</risdate><volume>14</volume><issue>24</issue><spage>8420</spage><epage>8429</epage><pages>8420-8429</pages><issn>0968-0896</issn><eissn>1464-3391</eissn><abstract>For advanced understanding of mechanism of chelating inhibitors.
We propose a two-metal binding model as a potential mechanism of chelating inhibitors against HIV integrase (HIV IN) represented by 2-hydroxy-3-heteroaryl acrylic acids (HHAAs). Potential inhibitors would bind to two metal ions in the active site of HIV IN to prevent human DNA from undergoing the integration reaction. Correlation of the results of metal (Mg
2+ and Mn
2+) titration studies with HIV IN inhibition for a series of active and inactive compounds provides support for the model. Results suggest Mg
2+ is an essential cofactor for chelating inhibitors.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>17005407</pmid><doi>10.1016/j.bmc.2006.08.043</doi><tpages>10</tpages></addata></record> |
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| ispartof | Bioorganic & medicinal chemistry, 2006-12, Vol.14 (24), p.8420-8429 |
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| subjects | Acrylates - chemical synthesis Acrylates - chemistry Acrylates - pharmacology Anti-HIV Agents - chemical synthesis Anti-HIV Agents - chemistry Anti-HIV Agents - pharmacology Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agents Binding Sites Biological and medical sciences Chelating Agents - chemical synthesis Chelating Agents - chemistry Chelating Agents - pharmacology Docking model Drug Design HIV Integrase - chemistry HIV Integrase - metabolism HIV integrase inhibitor HIV Integrase Inhibitors - chemical synthesis HIV Integrase Inhibitors - chemistry HIV Integrase Inhibitors - pharmacology HIV-1 - drug effects Human immunodeficiency virus Humans Inhibition mechanism Magnesium - metabolism Manganese - metabolism Medical sciences Metal affinity Models, Biological Models, Molecular Molecular Structure Pharmacology. Drug treatments Structure-Activity Relationship Two-metal binding model |
| title | A platform for designing HIV integrase inhibitors. Part 2: A two-metal binding model as a potential mechanism of HIV integrase inhibitors |
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