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Discovery and optimisation of potent, selective, ethanolamine inhibitors of bacterial phenylalanyl tRNA synthetase
High throughput screening of Staphylococcus aureus phenylalanyl tRNA synthetase (FRS) identified an ethanolamine as a sub-micromolar hit. Optimisation studies led to the enantiospecific lead 64, a single-figure nanomolar inhibitor. The inhibitor series shows selectivity with respect to the mammalian...
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| Published in: | Bioorganic & medicinal chemistry letters 2005-05, Vol.15 (9), p.2305-2309 |
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| Main Authors: | , , , , , , , , |
| Format: | Article |
| Language: | English |
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| cited_by | cdi_FETCH-LOGICAL-c384t-c820c5a884a6a762d5bbfa9ec067c24fd43fc3454aecaef11b7a49911d0000003 |
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| cites | cdi_FETCH-LOGICAL-c384t-c820c5a884a6a762d5bbfa9ec067c24fd43fc3454aecaef11b7a49911d0000003 |
| container_end_page | 2309 |
| container_issue | 9 |
| container_start_page | 2305 |
| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 15 |
| creator | Jarvest, Richard L. Erskine, Symon G. Forrest, Andrew K. Fosberry, Andrew P. Hibbs, Martin J. Jones, Joanna J. O’Hanlon, Peter J. Sheppard, Robert J. Worby, Angela |
| description | High throughput screening of
Staphylococcus aureus phenylalanyl tRNA synthetase (FRS) identified an ethanolamine as a sub-micromolar hit. Optimisation studies led to the enantiospecific lead
64, a single-figure nanomolar inhibitor. The inhibitor series shows selectivity with respect to the mammalian enzyme and the potential for broad spectrum bacterial FRS inhibition.
High throughput screening of
Staphylococcus aureus phenylalanyl tRNA synthetase (FRS) identified ethanolamine
1 as a sub-micromolar hit. Optimisation studies led to the enantiospecific lead
64, a single-figure nanomolar inhibitor. The inhibitor series shows selectivity with respect to the mammalian enzyme and the potential for broad spectrum bacterial FRS inhibition. |
| doi_str_mv | 10.1016/j.bmcl.2005.03.003 |
| format | article |
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Staphylococcus aureus phenylalanyl tRNA synthetase (FRS) identified an ethanolamine as a sub-micromolar hit. Optimisation studies led to the enantiospecific lead
64, a single-figure nanomolar inhibitor. The inhibitor series shows selectivity with respect to the mammalian enzyme and the potential for broad spectrum bacterial FRS inhibition.
High throughput screening of
Staphylococcus aureus phenylalanyl tRNA synthetase (FRS) identified ethanolamine
1 as a sub-micromolar hit. Optimisation studies led to the enantiospecific lead
64, a single-figure nanomolar inhibitor. The inhibitor series shows selectivity with respect to the mammalian enzyme and the potential for broad spectrum bacterial FRS inhibition.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2005.03.003</identifier><identifier>PMID: 15837314</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Animals ; Anti-Bacterial Agents - chemical synthesis ; Anti-Bacterial Agents - pharmacology ; Antibacterial agents ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Biological and medical sciences ; Drug Design ; Enzyme Inhibitors - chemical synthesis ; Enzyme Inhibitors - pharmacology ; Ethanolamines - chemical synthesis ; Ethanolamines - pharmacology ; Kinetics ; Mammals ; Medical sciences ; Microbial Sensitivity Tests ; Models, Molecular ; Pharmacology. Drug treatments ; Phenylalanine-tRNA Ligase - antagonists & inhibitors ; Sensitivity and Specificity ; Staphylococcus aureus - drug effects ; Staphylococcus aureus - enzymology ; Structure-Activity Relationship</subject><ispartof>Bioorganic & medicinal chemistry letters, 2005-05, Vol.15 (9), p.2305-2309</ispartof><rights>2005 Elsevier Ltd</rights><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c384t-c820c5a884a6a762d5bbfa9ec067c24fd43fc3454aecaef11b7a49911d0000003</citedby><cites>FETCH-LOGICAL-c384t-c820c5a884a6a762d5bbfa9ec067c24fd43fc3454aecaef11b7a49911d0000003</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16724178$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15837314$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jarvest, Richard L.</creatorcontrib><creatorcontrib>Erskine, Symon G.</creatorcontrib><creatorcontrib>Forrest, Andrew K.</creatorcontrib><creatorcontrib>Fosberry, Andrew P.</creatorcontrib><creatorcontrib>Hibbs, Martin J.</creatorcontrib><creatorcontrib>Jones, Joanna J.</creatorcontrib><creatorcontrib>O’Hanlon, Peter J.</creatorcontrib><creatorcontrib>Sheppard, Robert J.</creatorcontrib><creatorcontrib>Worby, Angela</creatorcontrib><title>Discovery and optimisation of potent, selective, ethanolamine inhibitors of bacterial phenylalanyl tRNA synthetase</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>High throughput screening of
Staphylococcus aureus phenylalanyl tRNA synthetase (FRS) identified an ethanolamine as a sub-micromolar hit. Optimisation studies led to the enantiospecific lead
64, a single-figure nanomolar inhibitor. The inhibitor series shows selectivity with respect to the mammalian enzyme and the potential for broad spectrum bacterial FRS inhibition.
High throughput screening of
Staphylococcus aureus phenylalanyl tRNA synthetase (FRS) identified ethanolamine
1 as a sub-micromolar hit. Optimisation studies led to the enantiospecific lead
64, a single-figure nanomolar inhibitor. The inhibitor series shows selectivity with respect to the mammalian enzyme and the potential for broad spectrum bacterial FRS inhibition.</description><subject>Animals</subject><subject>Anti-Bacterial Agents - chemical synthesis</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Antibacterial agents</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Biological and medical sciences</subject><subject>Drug Design</subject><subject>Enzyme Inhibitors - chemical synthesis</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Ethanolamines - chemical synthesis</subject><subject>Ethanolamines - pharmacology</subject><subject>Kinetics</subject><subject>Mammals</subject><subject>Medical sciences</subject><subject>Microbial Sensitivity Tests</subject><subject>Models, Molecular</subject><subject>Pharmacology. 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Antiinfectious agents. Antiparasitic agents</topic><topic>Biological and medical sciences</topic><topic>Drug Design</topic><topic>Enzyme Inhibitors - chemical synthesis</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Ethanolamines - chemical synthesis</topic><topic>Ethanolamines - pharmacology</topic><topic>Kinetics</topic><topic>Mammals</topic><topic>Medical sciences</topic><topic>Microbial Sensitivity Tests</topic><topic>Models, Molecular</topic><topic>Pharmacology. 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Staphylococcus aureus phenylalanyl tRNA synthetase (FRS) identified an ethanolamine as a sub-micromolar hit. Optimisation studies led to the enantiospecific lead
64, a single-figure nanomolar inhibitor. The inhibitor series shows selectivity with respect to the mammalian enzyme and the potential for broad spectrum bacterial FRS inhibition.
High throughput screening of
Staphylococcus aureus phenylalanyl tRNA synthetase (FRS) identified ethanolamine
1 as a sub-micromolar hit. Optimisation studies led to the enantiospecific lead
64, a single-figure nanomolar inhibitor. The inhibitor series shows selectivity with respect to the mammalian enzyme and the potential for broad spectrum bacterial FRS inhibition.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>15837314</pmid><doi>10.1016/j.bmcl.2005.03.003</doi><tpages>5</tpages></addata></record> |
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| ispartof | Bioorganic & medicinal chemistry letters, 2005-05, Vol.15 (9), p.2305-2309 |
| issn | 0960-894X 1464-3405 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_67749469 |
| source | Elsevier:Jisc Collections:Elsevier Read and Publish Agreement 2022-2024:Freedom Collection (Reading list) |
| subjects | Animals Anti-Bacterial Agents - chemical synthesis Anti-Bacterial Agents - pharmacology Antibacterial agents Antibiotics. Antiinfectious agents. Antiparasitic agents Biological and medical sciences Drug Design Enzyme Inhibitors - chemical synthesis Enzyme Inhibitors - pharmacology Ethanolamines - chemical synthesis Ethanolamines - pharmacology Kinetics Mammals Medical sciences Microbial Sensitivity Tests Models, Molecular Pharmacology. Drug treatments Phenylalanine-tRNA Ligase - antagonists & inhibitors Sensitivity and Specificity Staphylococcus aureus - drug effects Staphylococcus aureus - enzymology Structure-Activity Relationship |
| title | Discovery and optimisation of potent, selective, ethanolamine inhibitors of bacterial phenylalanyl tRNA synthetase |
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