Rapid Synthesis and In Situ Screening of Potent HIV-1 Protease Dimerization Inhibitors
A library of dimerization inhibitors of HIV-1 protease is described based on crosslinked interfacial peptides. The 54 component library was designed to contain two modifications to the starting structure, one each in the Northern and Southern fragments. A rapid synthesis and in situ screening method...
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| Veröffentlicht in: | Chemistry & biology 2006-04, Vol.13 (4), p.421-426 |
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| creator | Lee, Song-Gil Chmielewski, Jean |
| description | A library of dimerization inhibitors of HIV-1 protease is described based on crosslinked interfacial peptides. The 54 component library was designed to contain two modifications to the starting structure, one each in the Northern and Southern fragments. A rapid synthesis and in situ screening method in microtiter plates was developed to facilitate the generation and evaluation of the library members. More than 90% of the doubly modified agents were more potent than their respective singly mutated parent compounds, and five of the most potent dimerization inhibitors of HIV-1 protease described to date were identified. The free energy of binding for the combined two modifications was generally found to be additive, demonstrating the predictive value of earlier libraries. |
| doi_str_mv | 10.1016/j.chembiol.2006.02.012 |
| format | Article |
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The 54 component library was designed to contain two modifications to the starting structure, one each in the Northern and Southern fragments. A rapid synthesis and in situ screening method in microtiter plates was developed to facilitate the generation and evaluation of the library members. More than 90% of the doubly modified agents were more potent than their respective singly mutated parent compounds, and five of the most potent dimerization inhibitors of HIV-1 protease described to date were identified. The free energy of binding for the combined two modifications was generally found to be additive, demonstrating the predictive value of earlier libraries.</description><identifier>ISSN: 1074-5521</identifier><identifier>EISSN: 1879-1301</identifier><identifier>DOI: 10.1016/j.chembiol.2006.02.012</identifier><identifier>PMID: 16632254</identifier><language>eng</language><publisher>United States: Elsevier Ltd</publisher><subject>CHEMBIO ; Dimerization ; Drug Resistance, Viral ; HIV Protease Inhibitors - chemical synthesis ; HIV Protease Inhibitors - chemistry ; HIV Protease Inhibitors - pharmacology ; HIV-1 - drug effects ; HIV-1 - enzymology ; Humans ; In Vitro Techniques ; Microbial Sensitivity Tests ; Oligopeptides - chemical synthesis ; Oligopeptides - chemistry ; Oligopeptides - pharmacology ; Peptide Library ; Protein Structure, Quaternary - drug effects</subject><ispartof>Chemistry & biology, 2006-04, Vol.13 (4), p.421-426</ispartof><rights>2006 Elsevier Ltd</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c480t-f3d2b2e3b7f6b4259876dfa358636609fba049cfcf3a35b3c059f3abfec41493</citedby><cites>FETCH-LOGICAL-c480t-f3d2b2e3b7f6b4259876dfa358636609fba049cfcf3a35b3c059f3abfec41493</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1074552106000822$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16632254$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Song-Gil</creatorcontrib><creatorcontrib>Chmielewski, Jean</creatorcontrib><title>Rapid Synthesis and In Situ Screening of Potent HIV-1 Protease Dimerization Inhibitors</title><title>Chemistry & biology</title><addtitle>Chem Biol</addtitle><description>A library of dimerization inhibitors of HIV-1 protease is described based on crosslinked interfacial peptides. 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The free energy of binding for the combined two modifications was generally found to be additive, demonstrating the predictive value of earlier libraries.</description><subject>CHEMBIO</subject><subject>Dimerization</subject><subject>Drug Resistance, Viral</subject><subject>HIV Protease Inhibitors - chemical synthesis</subject><subject>HIV Protease Inhibitors - chemistry</subject><subject>HIV Protease Inhibitors - pharmacology</subject><subject>HIV-1 - drug effects</subject><subject>HIV-1 - enzymology</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Microbial Sensitivity Tests</subject><subject>Oligopeptides - chemical synthesis</subject><subject>Oligopeptides - chemistry</subject><subject>Oligopeptides - pharmacology</subject><subject>Peptide Library</subject><subject>Protein Structure, Quaternary - drug effects</subject><issn>1074-5521</issn><issn>1879-1301</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEtv1DAUhS0Eog_4C5VX7JJe24mT7EDl0ZEqUTFVt5btXDMeTezB9lQqvx5XM4glq_vQOffofoRcMWgZMHm9be0GF-PjruUAsgXeAuOvyDkbh6lhAtjr2sPQNX3P2Rm5yHkLAGyc5FtyxqQUnPfdOXn8ofd-puvnUDaYfaY6zHQV6NqXA13bhBh8-Emjo_exYCj0dvXYMHqf6qQz0s9-weR_6-JjqL6NN77ElN-RN07vMr4_1Uvy8PXLw81tc_f92-rm011juxFK48TMDUdhBidNx_tpHOTstOhHKaSEyRkN3WSddaIujbDQT7U1Dm3Huklckg_Hs_sUfx0wF7X4bHG30wHjISs5jPVhMVShPAptijkndGqf_KLTs2KgXoCqrfoLVL0AVcBVBVqNV6eEg1lw_mc7EayCj0cB1jefPCaVrcdgcfYJbVFz9P_L-AMFLIp2</recordid><startdate>20060401</startdate><enddate>20060401</enddate><creator>Lee, Song-Gil</creator><creator>Chmielewski, Jean</creator><general>Elsevier Ltd</general><scope>6I.</scope><scope>AAFTH</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>7X8</scope></search><sort><creationdate>20060401</creationdate><title>Rapid Synthesis and In Situ Screening of Potent HIV-1 Protease Dimerization Inhibitors</title><author>Lee, Song-Gil ; Chmielewski, Jean</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c480t-f3d2b2e3b7f6b4259876dfa358636609fba049cfcf3a35b3c059f3abfec41493</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>CHEMBIO</topic><topic>Dimerization</topic><topic>Drug Resistance, Viral</topic><topic>HIV Protease Inhibitors - chemical synthesis</topic><topic>HIV Protease Inhibitors - chemistry</topic><topic>HIV Protease Inhibitors - pharmacology</topic><topic>HIV-1 - drug effects</topic><topic>HIV-1 - enzymology</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>Microbial Sensitivity Tests</topic><topic>Oligopeptides - chemical synthesis</topic><topic>Oligopeptides - chemistry</topic><topic>Oligopeptides - pharmacology</topic><topic>Peptide Library</topic><topic>Protein Structure, Quaternary - drug effects</topic><toplevel>online_resources</toplevel><creatorcontrib>Lee, Song-Gil</creatorcontrib><creatorcontrib>Chmielewski, Jean</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Chemistry & biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Song-Gil</au><au>Chmielewski, Jean</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rapid Synthesis and In Situ Screening of Potent HIV-1 Protease Dimerization Inhibitors</atitle><jtitle>Chemistry & biology</jtitle><addtitle>Chem Biol</addtitle><date>2006-04-01</date><risdate>2006</risdate><volume>13</volume><issue>4</issue><spage>421</spage><epage>426</epage><pages>421-426</pages><issn>1074-5521</issn><eissn>1879-1301</eissn><abstract>A library of dimerization inhibitors of HIV-1 protease is described based on crosslinked interfacial peptides. 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| ispartof | Chemistry & biology, 2006-04, Vol.13 (4), p.421-426 |
| issn | 1074-5521 1879-1301 |
| language | eng |
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| source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; EZB-FREE-00999 freely available EZB journals; Free Full-Text Journals in Chemistry |
| subjects | CHEMBIO Dimerization Drug Resistance, Viral HIV Protease Inhibitors - chemical synthesis HIV Protease Inhibitors - chemistry HIV Protease Inhibitors - pharmacology HIV-1 - drug effects HIV-1 - enzymology Humans In Vitro Techniques Microbial Sensitivity Tests Oligopeptides - chemical synthesis Oligopeptides - chemistry Oligopeptides - pharmacology Peptide Library Protein Structure, Quaternary - drug effects |
| title | Rapid Synthesis and In Situ Screening of Potent HIV-1 Protease Dimerization Inhibitors |
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