Vinyl Sulfones: Inhibitors of SrtA, a Transpeptidase Required for Cell Wall Protein Anchoring and Virulence in Staphylococcus aureus
Several small molecule vinyl sulfones were found to exhibit irreversible time-dependent inhibition of the Staphylococcus aureus sortase SrtA in vitro. A representative of these compounds was shown to impair the ability of S. aureus bacteria to bind fibronectin-coated surfaces through in vivo inhibit...
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| Veröffentlicht in: | Journal of the American Chemical Society 2004-03, Vol.126 (11), p.3404-3405 |
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| container_end_page | 3405 |
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| container_issue | 11 |
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| container_title | Journal of the American Chemical Society |
| container_volume | 126 |
| creator | Frankel, Brenda A Bentley, Matthew Kruger, Ryan G McCafferty, Dewey G |
| description | Several small molecule vinyl sulfones were found to exhibit irreversible time-dependent inhibition of the Staphylococcus aureus sortase SrtA in vitro. A representative of these compounds was shown to impair the ability of S. aureus bacteria to bind fibronectin-coated surfaces through in vivo inhibition of SrtA-mediated linkage of fibronectin to the cell surface. These data highlight the potential use of small molecule vinyl sulfones as chemotherapeutics to prevent adhesion to and colonization of host tissues during S. aureus infection. |
| doi_str_mv | 10.1021/ja0390294 |
| format | Article |
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A representative of these compounds was shown to impair the ability of S. aureus bacteria to bind fibronectin-coated surfaces through in vivo inhibition of SrtA-mediated linkage of fibronectin to the cell surface. 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Am. Chem. Soc</addtitle><description>Several small molecule vinyl sulfones were found to exhibit irreversible time-dependent inhibition of the Staphylococcus aureus sortase SrtA in vitro. A representative of these compounds was shown to impair the ability of S. aureus bacteria to bind fibronectin-coated surfaces through in vivo inhibition of SrtA-mediated linkage of fibronectin to the cell surface. These data highlight the potential use of small molecule vinyl sulfones as chemotherapeutics to prevent adhesion to and colonization of host tissues during S. aureus infection.</description><subject>Aminoacyltransferases - antagonists & inhibitors</subject><subject>Aminoacyltransferases - metabolism</subject><subject>Bacterial Proteins</subject><subject>Biological and medical sciences</subject><subject>Cell Wall - enzymology</subject><subject>Cell Wall - physiology</subject><subject>Cysteine Endopeptidases</subject><subject>Enzyme Inhibitors - chemistry</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Mechanisms. Catalysis. Electron transfer. Models</subject><subject>Molecular biophysics</subject><subject>Physical chemistry in biology</subject><subject>Staphylococcus aureus - drug effects</subject><subject>Staphylococcus aureus - enzymology</subject><subject>Staphylococcus aureus - pathogenicity</subject><subject>Sulfones - chemistry</subject><subject>Sulfones - pharmacology</subject><subject>Virulence</subject><issn>0002-7863</issn><issn>1520-5126</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkMtuEzEUhi0EomlhwQsgb0CqxBRfxnPpLgptaalE1ISytM54PMRhYk_tsdTs2CFekyfBKFHLgs05Ovo__Tr6EHpFyQkljL5fA-E1YXX-BE2oYCQTlBVP0YQQwrKyKvgBOgxhnc6cVfQ5OqCCMJELMkE_b43d9ngR-85ZHU5___iFL-3KNGZ0PmDX4YUfp-8w4KUHGwY9jKaFoPGNvovG6xZ3zuOZ7nv8FdKYezdqY_HUqpXzxn7DYFt8a3zstVUap2gxwrDa9k45pWLAEL2O4QV61kEf9Mv9PkJfzs-Ws4_Z9eeLy9n0OgNe1mMGbVNR1Va8K4RuoWINp2lxUeeqKYUiwFmrqragVakVUYo2vCyAasaKiivKj9DbXe_g3V3UYZQbE1R6H6x2MciSljxnNUng8Q5U3oXgdScHbzbgt5IS-de6fLCe2Nf70thsdPtI7jUn4M0egKCg75JKZcI_nKhrXpSJy3acCaO-f8jBf5cpLYVczhdyeXM1_3Tx4VzWj72ggly76G1y958H_wCYc6cA</recordid><startdate>20040324</startdate><enddate>20040324</enddate><creator>Frankel, Brenda A</creator><creator>Bentley, Matthew</creator><creator>Kruger, Ryan G</creator><creator>McCafferty, Dewey G</creator><general>American Chemical Society</general><scope>BSCLL</scope><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>7X8</scope></search><sort><creationdate>20040324</creationdate><title>Vinyl Sulfones: Inhibitors of SrtA, a Transpeptidase Required for Cell Wall Protein Anchoring and Virulence in Staphylococcus aureus</title><author>Frankel, Brenda A ; Bentley, Matthew ; Kruger, Ryan G ; McCafferty, Dewey G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a379t-adb81cd83f65eda82b31da83594cb75c0a32dc8d6187ec0cc1b376a1e22683c13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Aminoacyltransferases - antagonists & inhibitors</topic><topic>Aminoacyltransferases - metabolism</topic><topic>Bacterial Proteins</topic><topic>Biological and medical sciences</topic><topic>Cell Wall - enzymology</topic><topic>Cell Wall - physiology</topic><topic>Cysteine Endopeptidases</topic><topic>Enzyme Inhibitors - chemistry</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Mechanisms. Catalysis. Electron transfer. Models</topic><topic>Molecular biophysics</topic><topic>Physical chemistry in biology</topic><topic>Staphylococcus aureus - drug effects</topic><topic>Staphylococcus aureus - enzymology</topic><topic>Staphylococcus aureus - pathogenicity</topic><topic>Sulfones - chemistry</topic><topic>Sulfones - pharmacology</topic><topic>Virulence</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Frankel, Brenda A</creatorcontrib><creatorcontrib>Bentley, Matthew</creatorcontrib><creatorcontrib>Kruger, Ryan G</creatorcontrib><creatorcontrib>McCafferty, Dewey G</creatorcontrib><collection>Istex</collection><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>MEDLINE - Academic</collection><jtitle>Journal of the American Chemical Society</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Frankel, Brenda A</au><au>Bentley, Matthew</au><au>Kruger, Ryan G</au><au>McCafferty, Dewey G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Vinyl Sulfones: Inhibitors of SrtA, a Transpeptidase Required for Cell Wall Protein Anchoring and Virulence in Staphylococcus aureus</atitle><jtitle>Journal of the American Chemical Society</jtitle><addtitle>J. Am. Chem. Soc</addtitle><date>2004-03-24</date><risdate>2004</risdate><volume>126</volume><issue>11</issue><spage>3404</spage><epage>3405</epage><pages>3404-3405</pages><issn>0002-7863</issn><eissn>1520-5126</eissn><coden>JACSAT</coden><abstract>Several small molecule vinyl sulfones were found to exhibit irreversible time-dependent inhibition of the Staphylococcus aureus sortase SrtA in vitro. A representative of these compounds was shown to impair the ability of S. aureus bacteria to bind fibronectin-coated surfaces through in vivo inhibition of SrtA-mediated linkage of fibronectin to the cell surface. These data highlight the potential use of small molecule vinyl sulfones as chemotherapeutics to prevent adhesion to and colonization of host tissues during S. aureus infection.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>15025450</pmid><doi>10.1021/ja0390294</doi><tpages>2</tpages></addata></record> |
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| ispartof | Journal of the American Chemical Society, 2004-03, Vol.126 (11), p.3404-3405 |
| issn | 0002-7863 1520-5126 |
| language | eng |
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| source | ACS Publications; MEDLINE |
| subjects | Aminoacyltransferases - antagonists & inhibitors Aminoacyltransferases - metabolism Bacterial Proteins Biological and medical sciences Cell Wall - enzymology Cell Wall - physiology Cysteine Endopeptidases Enzyme Inhibitors - chemistry Enzyme Inhibitors - pharmacology Fundamental and applied biological sciences. Psychology Mechanisms. Catalysis. Electron transfer. Models Molecular biophysics Physical chemistry in biology Staphylococcus aureus - drug effects Staphylococcus aureus - enzymology Staphylococcus aureus - pathogenicity Sulfones - chemistry Sulfones - pharmacology Virulence |
| title | Vinyl Sulfones: Inhibitors of SrtA, a Transpeptidase Required for Cell Wall Protein Anchoring and Virulence in Staphylococcus aureus |
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