Discovery of indolyl-containing peptides as novel antibacterial agents targeting tryptophanyl-tRNA synthetase
There is an urgent need for antibiotics with novel structures and unexploited targets to counteract bacterial resistance. Novel tryptophanyl-tRNA synthetase inhibitors were discovered based on virtual screening, surface plasmon resonance binding, enzymatic activity assay and antibacterial activity e...
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| Veröffentlicht in: | Future medicinal chemistry 2020-05, Vol.12 (10), p.877-896 |
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| container_title | Future medicinal chemistry |
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| creator | Zhang, Shuo Qiu, Xiaodan Wang, Ran Sun, Lianqi Zhu, Zhiling Shan, Guangzhi Li, Zhuorong |
| description | There is an urgent need for antibiotics with novel structures and unexploited targets to counteract bacterial resistance.
Novel tryptophanyl-tRNA synthetase inhibitors were discovered based on virtual screening, surface plasmon resonance binding, enzymatic activity assay and antibacterial activity evaluation. Of the 29 peptide derivatives tested for antibacterial activity, some inhibited the growth of both
and
.
and
exhibited antibacterial activity against methicillin-resistant
NRS384 at an 8 μg/ml minimum inhibitory concentration.
snugly docked into the active site, explaining its improved inhibitory activity.
Our results provide us with new structural clues to develop more potent tryptophanyl-tRNA synthetase inhibitors and lay a solid foundation for future drug design efforts. |
| doi_str_mv | 10.4155/fmc-2020-0016 |
| format | Article |
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Novel tryptophanyl-tRNA synthetase inhibitors were discovered based on virtual screening, surface plasmon resonance binding, enzymatic activity assay and antibacterial activity evaluation. Of the 29 peptide derivatives tested for antibacterial activity, some inhibited the growth of both
and
.
and
exhibited antibacterial activity against methicillin-resistant
NRS384 at an 8 μg/ml minimum inhibitory concentration.
snugly docked into the active site, explaining its improved inhibitory activity.
Our results provide us with new structural clues to develop more potent tryptophanyl-tRNA synthetase inhibitors and lay a solid foundation for future drug design efforts.</description><identifier>ISSN: 1756-8919</identifier><identifier>EISSN: 1756-8927</identifier><identifier>DOI: 10.4155/fmc-2020-0016</identifier><identifier>PMID: 32312096</identifier><language>eng</language><publisher>England: Newlands Press Ltd</publisher><subject>Amino acids ; Anti-Bacterial Agents - chemical synthesis ; Anti-Bacterial Agents - chemistry ; Anti-Bacterial Agents - pharmacology ; Antibacterial activity ; antibacterial agent ; Antibacterial agents ; antibiotic resistance ; Antibiotics ; Bacteria ; Bacterial infections ; Design ; Drug development ; Drug Discovery ; Drug resistance ; Enzymatic activity ; enzyme inhibitor ; Enzyme Inhibitors - chemical synthesis ; Enzyme Inhibitors - chemistry ; Enzyme Inhibitors - pharmacology ; Enzymes ; Gram-positive bacteria ; Indoles - chemistry ; Indoles - pharmacology ; Libraries ; Methicillin ; Microbial Sensitivity Tests ; Minimum inhibitory concentration ; Molecular Structure ; NMR ; Nuclear magnetic resonance ; Peptides - chemical synthesis ; Peptides - chemistry ; Peptides - pharmacology ; Protein synthesis ; Proteins ; Staphylococcus aureus - drug effects ; Staphylococcus epidermidis - drug effects ; Surface plasmon resonance ; tripeptide ; tRNA ; Tryptophan-tRNA ligase ; Tryptophan-tRNA Ligase - antagonists & inhibitors ; Tryptophan-tRNA Ligase - metabolism ; tryptophanyl-tRNA synthetase</subject><ispartof>Future medicinal chemistry, 2020-05, Vol.12 (10), p.877-896</ispartof><rights>2020 Institute of Medicinal Biotechnology CAMS & PUMC</rights><rights>2020. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c410t-2142b8ae2588c71890d525ec840c04495f6358ebbe85a8cf46a4a4c11881c1b63</citedby><cites>FETCH-LOGICAL-c410t-2142b8ae2588c71890d525ec840c04495f6358ebbe85a8cf46a4a4c11881c1b63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,27907,27908</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32312096$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Shuo</creatorcontrib><creatorcontrib>Qiu, Xiaodan</creatorcontrib><creatorcontrib>Wang, Ran</creatorcontrib><creatorcontrib>Sun, Lianqi</creatorcontrib><creatorcontrib>Zhu, Zhiling</creatorcontrib><creatorcontrib>Shan, Guangzhi</creatorcontrib><creatorcontrib>Li, Zhuorong</creatorcontrib><title>Discovery of indolyl-containing peptides as novel antibacterial agents targeting tryptophanyl-tRNA synthetase</title><title>Future medicinal chemistry</title><addtitle>Future Med Chem</addtitle><description>There is an urgent need for antibiotics with novel structures and unexploited targets to counteract bacterial resistance.
Novel tryptophanyl-tRNA synthetase inhibitors were discovered based on virtual screening, surface plasmon resonance binding, enzymatic activity assay and antibacterial activity evaluation. Of the 29 peptide derivatives tested for antibacterial activity, some inhibited the growth of both
and
.
and
exhibited antibacterial activity against methicillin-resistant
NRS384 at an 8 μg/ml minimum inhibitory concentration.
snugly docked into the active site, explaining its improved inhibitory activity.
Our results provide us with new structural clues to develop more potent tryptophanyl-tRNA synthetase inhibitors and lay a solid foundation for future drug design efforts.</description><subject>Amino acids</subject><subject>Anti-Bacterial Agents - chemical synthesis</subject><subject>Anti-Bacterial Agents - chemistry</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Antibacterial activity</subject><subject>antibacterial agent</subject><subject>Antibacterial agents</subject><subject>antibiotic resistance</subject><subject>Antibiotics</subject><subject>Bacteria</subject><subject>Bacterial infections</subject><subject>Design</subject><subject>Drug development</subject><subject>Drug Discovery</subject><subject>Drug resistance</subject><subject>Enzymatic activity</subject><subject>enzyme inhibitor</subject><subject>Enzyme Inhibitors - chemical synthesis</subject><subject>Enzyme Inhibitors - chemistry</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Enzymes</subject><subject>Gram-positive bacteria</subject><subject>Indoles - chemistry</subject><subject>Indoles - pharmacology</subject><subject>Libraries</subject><subject>Methicillin</subject><subject>Microbial Sensitivity Tests</subject><subject>Minimum inhibitory concentration</subject><subject>Molecular Structure</subject><subject>NMR</subject><subject>Nuclear magnetic resonance</subject><subject>Peptides - chemical synthesis</subject><subject>Peptides - chemistry</subject><subject>Peptides - pharmacology</subject><subject>Protein synthesis</subject><subject>Proteins</subject><subject>Staphylococcus aureus - drug effects</subject><subject>Staphylococcus epidermidis - drug effects</subject><subject>Surface plasmon resonance</subject><subject>tripeptide</subject><subject>tRNA</subject><subject>Tryptophan-tRNA ligase</subject><subject>Tryptophan-tRNA Ligase - antagonists & inhibitors</subject><subject>Tryptophan-tRNA Ligase - metabolism</subject><subject>tryptophanyl-tRNA synthetase</subject><issn>1756-8919</issn><issn>1756-8927</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kU1LJDEQhsOysso4x70uDXvZS2s-e5LjoO4qDAqi55DOVI-R7qQ3SQv9780w6kGwLlUFT71U1YvQT4LPOBHivBtsTTHFNcak-YZOyEo0tVR09f2jJuoYLVN6xiUYlaoRP9Axo4xQrJoTNFy6ZMMLxLkKXeX8NvRzX9vgs3He-V01wpjdFlJlUuUL2FfGZ9camyE6U7od-JyqbOIO8n4gx3nMYXwyvgjl-9t1lWafnyCbBKfoqDN9guVbXqDHv1cPF9f15u7fzcV6U1tOcK4p4bSVBqiQ0q6IVHgrqAArObaYcyW6hgkJbQtSGGk73hhuuCVESmJJ27AF-nPQHWP4P0HKeihnQt8bD2FKmjLFsOCSiYL-_oQ-hyn6sp2mgnBGm5VihaoPlI0hpQidHqMbTJw1wXpvhS5W6L0Vem9F4X-9qU7tANsP-v3xBVAHoJvyFCFZB96CPnRlwlnn4QvxV-CWmJs</recordid><startdate>20200501</startdate><enddate>20200501</enddate><creator>Zhang, Shuo</creator><creator>Qiu, Xiaodan</creator><creator>Wang, Ran</creator><creator>Sun, Lianqi</creator><creator>Zhu, Zhiling</creator><creator>Shan, Guangzhi</creator><creator>Li, Zhuorong</creator><general>Newlands Press Ltd</general><general>Newlands Press</general><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20200501</creationdate><title>Discovery of indolyl-containing peptides as novel antibacterial agents targeting tryptophanyl-tRNA synthetase</title><author>Zhang, Shuo ; Qiu, Xiaodan ; Wang, Ran ; Sun, Lianqi ; Zhu, Zhiling ; Shan, Guangzhi ; Li, Zhuorong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c410t-2142b8ae2588c71890d525ec840c04495f6358ebbe85a8cf46a4a4c11881c1b63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Amino acids</topic><topic>Anti-Bacterial Agents - chemical synthesis</topic><topic>Anti-Bacterial Agents - chemistry</topic><topic>Anti-Bacterial Agents - pharmacology</topic><topic>Antibacterial activity</topic><topic>antibacterial agent</topic><topic>Antibacterial agents</topic><topic>antibiotic resistance</topic><topic>Antibiotics</topic><topic>Bacteria</topic><topic>Bacterial infections</topic><topic>Design</topic><topic>Drug development</topic><topic>Drug Discovery</topic><topic>Drug resistance</topic><topic>Enzymatic activity</topic><topic>enzyme inhibitor</topic><topic>Enzyme Inhibitors - chemical synthesis</topic><topic>Enzyme Inhibitors - chemistry</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Enzymes</topic><topic>Gram-positive bacteria</topic><topic>Indoles - chemistry</topic><topic>Indoles - pharmacology</topic><topic>Libraries</topic><topic>Methicillin</topic><topic>Microbial Sensitivity Tests</topic><topic>Minimum inhibitory concentration</topic><topic>Molecular Structure</topic><topic>NMR</topic><topic>Nuclear magnetic resonance</topic><topic>Peptides - chemical synthesis</topic><topic>Peptides - chemistry</topic><topic>Peptides - pharmacology</topic><topic>Protein synthesis</topic><topic>Proteins</topic><topic>Staphylococcus aureus - drug effects</topic><topic>Staphylococcus epidermidis - drug effects</topic><topic>Surface plasmon resonance</topic><topic>tripeptide</topic><topic>tRNA</topic><topic>Tryptophan-tRNA ligase</topic><topic>Tryptophan-tRNA Ligase - antagonists & inhibitors</topic><topic>Tryptophan-tRNA Ligase - metabolism</topic><topic>tryptophanyl-tRNA synthetase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Shuo</creatorcontrib><creatorcontrib>Qiu, Xiaodan</creatorcontrib><creatorcontrib>Wang, Ran</creatorcontrib><creatorcontrib>Sun, Lianqi</creatorcontrib><creatorcontrib>Zhu, Zhiling</creatorcontrib><creatorcontrib>Shan, Guangzhi</creatorcontrib><creatorcontrib>Li, Zhuorong</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection (ProQuest)</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Future medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Shuo</au><au>Qiu, Xiaodan</au><au>Wang, Ran</au><au>Sun, Lianqi</au><au>Zhu, Zhiling</au><au>Shan, Guangzhi</au><au>Li, Zhuorong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Discovery of indolyl-containing peptides as novel antibacterial agents targeting tryptophanyl-tRNA synthetase</atitle><jtitle>Future medicinal chemistry</jtitle><addtitle>Future Med Chem</addtitle><date>2020-05-01</date><risdate>2020</risdate><volume>12</volume><issue>10</issue><spage>877</spage><epage>896</epage><pages>877-896</pages><issn>1756-8919</issn><eissn>1756-8927</eissn><abstract>There is an urgent need for antibiotics with novel structures and unexploited targets to counteract bacterial resistance.
Novel tryptophanyl-tRNA synthetase inhibitors were discovered based on virtual screening, surface plasmon resonance binding, enzymatic activity assay and antibacterial activity evaluation. Of the 29 peptide derivatives tested for antibacterial activity, some inhibited the growth of both
and
.
and
exhibited antibacterial activity against methicillin-resistant
NRS384 at an 8 μg/ml minimum inhibitory concentration.
snugly docked into the active site, explaining its improved inhibitory activity.
Our results provide us with new structural clues to develop more potent tryptophanyl-tRNA synthetase inhibitors and lay a solid foundation for future drug design efforts.</abstract><cop>England</cop><pub>Newlands Press Ltd</pub><pmid>32312096</pmid><doi>10.4155/fmc-2020-0016</doi><tpages>20</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Future medicinal chemistry, 2020-05, Vol.12 (10), p.877-896 |
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| subjects | Amino acids Anti-Bacterial Agents - chemical synthesis Anti-Bacterial Agents - chemistry Anti-Bacterial Agents - pharmacology Antibacterial activity antibacterial agent Antibacterial agents antibiotic resistance Antibiotics Bacteria Bacterial infections Design Drug development Drug Discovery Drug resistance Enzymatic activity enzyme inhibitor Enzyme Inhibitors - chemical synthesis Enzyme Inhibitors - chemistry Enzyme Inhibitors - pharmacology Enzymes Gram-positive bacteria Indoles - chemistry Indoles - pharmacology Libraries Methicillin Microbial Sensitivity Tests Minimum inhibitory concentration Molecular Structure NMR Nuclear magnetic resonance Peptides - chemical synthesis Peptides - chemistry Peptides - pharmacology Protein synthesis Proteins Staphylococcus aureus - drug effects Staphylococcus epidermidis - drug effects Surface plasmon resonance tripeptide tRNA Tryptophan-tRNA ligase Tryptophan-tRNA Ligase - antagonists & inhibitors Tryptophan-tRNA Ligase - metabolism tryptophanyl-tRNA synthetase |
| title | Discovery of indolyl-containing peptides as novel antibacterial agents targeting tryptophanyl-tRNA synthetase |
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