Antibiotic evaluation and in vivo analysis of alkynyl Coenzyme A antimetabolites in Escherichia coli
A panel of pantetheine analogues was synthesized and the mechanism of their differential activity against Escherichia coli was probed with a series of kinetic and in vivo assays. The results have implications on the purported mode of action of this class of antibiotics. Pantothenamides have been the...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry 2008-11, Vol.18 (22), p.5991-5994 |
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| container_title | Bioorganic & medicinal chemistry |
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| creator | Mercer, Andrew C. Meier, Jordan L. Hur, Gene H. Smith, Andrew R. Burkart, Michael D. |
| description | A panel of pantetheine analogues was synthesized and the mechanism of their differential activity against
Escherichia coli was probed with a series of kinetic and in vivo assays. The results have implications on the purported mode of action of this class of antibiotics.
Pantothenamides have been the subject of much study as potential inhibitors of CoA and carrier protein dependent biosynthetic pathways. Based on an initial observation of growth inhibition in
Escherichia coli by
3, we have synthesized a small panel of pantetheine analogues and re-examined the inhibitory properties of this class of antibiotics with an emphasis on understanding the ability of these compounds to act as substrates of native CoA and carrier protein utilizing biosynthetic pathways. Our findings suggest that a secondary structure–activity relationship is an important factor in the antibiotic activity of these compounds. |
| doi_str_mv | 10.1016/j.bmcl.2008.07.078 |
| format | Article |
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Escherichia coli was probed with a series of kinetic and in vivo assays. The results have implications on the purported mode of action of this class of antibiotics.
Pantothenamides have been the subject of much study as potential inhibitors of CoA and carrier protein dependent biosynthetic pathways. Based on an initial observation of growth inhibition in
Escherichia coli by
3, we have synthesized a small panel of pantetheine analogues and re-examined the inhibitory properties of this class of antibiotics with an emphasis on understanding the ability of these compounds to act as substrates of native CoA and carrier protein utilizing biosynthetic pathways. Our findings suggest that a secondary structure–activity relationship is an important factor in the antibiotic activity of these compounds.</description><identifier>ISSN: 0960-894X</identifier><identifier>ISSN: 0968-0896</identifier><identifier>EISSN: 1464-3405</identifier><identifier>EISSN: 1464-3391</identifier><identifier>DOI: 10.1016/j.bmcl.2008.07.078</identifier><identifier>PMID: 18701278</identifier><language>eng</language><publisher>Amsterdam: Elsevier Ltd</publisher><subject>Aldehyde-Lyases - analysis ; Aldehyde-Lyases - metabolism ; Anti-Bacterial Agents - metabolism ; Antibacterial agents ; Antibiotic ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antimetabolites - metabolism ; Biological and medical sciences ; Coenzyme A ; Coenzyme A - metabolism ; Combinatorial Chemistry Techniques ; Cytochrome P-450 Enzyme System - analysis ; Cytochrome P-450 Enzyme System - metabolism ; Escherichia coli ; Escherichia coli - enzymology ; Escherichia coli - metabolism ; Fatty acid ; Medical sciences ; Molecular Structure ; Pantetheine - analogs & derivatives ; Pantetheine - chemical synthesis ; Pantetheine - chemistry ; Pantetheine - metabolism ; Pantothenamides ; Pharmacology. Drug treatments ; Structure-Activity Relationship ; Structure–activity relationships</subject><ispartof>Bioorganic & medicinal chemistry, 2008-11, Vol.18 (22), p.5991-5994</ispartof><rights>2008 Elsevier Ltd</rights><rights>2009 INIST-CNRS</rights><rights>2008 Elsevier Ltd. All rights reserved. 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c514t-9d8ff84f2ef0b45052a9d01a14157eaf73468784e35d1016526171d3371363353</citedby><cites>FETCH-LOGICAL-c514t-9d8ff84f2ef0b45052a9d01a14157eaf73468784e35d1016526171d3371363353</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bmcl.2008.07.078$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20887565$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18701278$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mercer, Andrew C.</creatorcontrib><creatorcontrib>Meier, Jordan L.</creatorcontrib><creatorcontrib>Hur, Gene H.</creatorcontrib><creatorcontrib>Smith, Andrew R.</creatorcontrib><creatorcontrib>Burkart, Michael D.</creatorcontrib><title>Antibiotic evaluation and in vivo analysis of alkynyl Coenzyme A antimetabolites in Escherichia coli</title><title>Bioorganic & medicinal chemistry</title><addtitle>Bioorg Med Chem Lett</addtitle><description>A panel of pantetheine analogues was synthesized and the mechanism of their differential activity against
Escherichia coli was probed with a series of kinetic and in vivo assays. The results have implications on the purported mode of action of this class of antibiotics.
Pantothenamides have been the subject of much study as potential inhibitors of CoA and carrier protein dependent biosynthetic pathways. Based on an initial observation of growth inhibition in
Escherichia coli by
3, we have synthesized a small panel of pantetheine analogues and re-examined the inhibitory properties of this class of antibiotics with an emphasis on understanding the ability of these compounds to act as substrates of native CoA and carrier protein utilizing biosynthetic pathways. Our findings suggest that a secondary structure–activity relationship is an important factor in the antibiotic activity of these compounds.</description><subject>Aldehyde-Lyases - analysis</subject><subject>Aldehyde-Lyases - metabolism</subject><subject>Anti-Bacterial Agents - metabolism</subject><subject>Antibacterial agents</subject><subject>Antibiotic</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antimetabolites - metabolism</subject><subject>Biological and medical sciences</subject><subject>Coenzyme A</subject><subject>Coenzyme A - metabolism</subject><subject>Combinatorial Chemistry Techniques</subject><subject>Cytochrome P-450 Enzyme System - analysis</subject><subject>Cytochrome P-450 Enzyme System - metabolism</subject><subject>Escherichia coli</subject><subject>Escherichia coli - enzymology</subject><subject>Escherichia coli - metabolism</subject><subject>Fatty acid</subject><subject>Medical sciences</subject><subject>Molecular Structure</subject><subject>Pantetheine - analogs & derivatives</subject><subject>Pantetheine - chemical synthesis</subject><subject>Pantetheine - chemistry</subject><subject>Pantetheine - metabolism</subject><subject>Pantothenamides</subject><subject>Pharmacology. 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Antiinfectious agents. Antiparasitic agents</topic><topic>Antimetabolites - metabolism</topic><topic>Biological and medical sciences</topic><topic>Coenzyme A</topic><topic>Coenzyme A - metabolism</topic><topic>Combinatorial Chemistry Techniques</topic><topic>Cytochrome P-450 Enzyme System - analysis</topic><topic>Cytochrome P-450 Enzyme System - metabolism</topic><topic>Escherichia coli</topic><topic>Escherichia coli - enzymology</topic><topic>Escherichia coli - metabolism</topic><topic>Fatty acid</topic><topic>Medical sciences</topic><topic>Molecular Structure</topic><topic>Pantetheine - analogs & derivatives</topic><topic>Pantetheine - chemical synthesis</topic><topic>Pantetheine - chemistry</topic><topic>Pantetheine - metabolism</topic><topic>Pantothenamides</topic><topic>Pharmacology. Drug treatments</topic><topic>Structure-Activity Relationship</topic><topic>Structure–activity relationships</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mercer, Andrew C.</creatorcontrib><creatorcontrib>Meier, Jordan L.</creatorcontrib><creatorcontrib>Hur, Gene H.</creatorcontrib><creatorcontrib>Smith, Andrew R.</creatorcontrib><creatorcontrib>Burkart, Michael D.</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>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Bioorganic & medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mercer, Andrew C.</au><au>Meier, Jordan L.</au><au>Hur, Gene H.</au><au>Smith, Andrew R.</au><au>Burkart, Michael D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antibiotic evaluation and in vivo analysis of alkynyl Coenzyme A antimetabolites in Escherichia coli</atitle><jtitle>Bioorganic & medicinal chemistry</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2008-11-15</date><risdate>2008</risdate><volume>18</volume><issue>22</issue><spage>5991</spage><epage>5994</epage><pages>5991-5994</pages><issn>0960-894X</issn><issn>0968-0896</issn><eissn>1464-3405</eissn><eissn>1464-3391</eissn><abstract>A panel of pantetheine analogues was synthesized and the mechanism of their differential activity against
Escherichia coli was probed with a series of kinetic and in vivo assays. The results have implications on the purported mode of action of this class of antibiotics.
Pantothenamides have been the subject of much study as potential inhibitors of CoA and carrier protein dependent biosynthetic pathways. Based on an initial observation of growth inhibition in
Escherichia coli by
3, we have synthesized a small panel of pantetheine analogues and re-examined the inhibitory properties of this class of antibiotics with an emphasis on understanding the ability of these compounds to act as substrates of native CoA and carrier protein utilizing biosynthetic pathways. Our findings suggest that a secondary structure–activity relationship is an important factor in the antibiotic activity of these compounds.</abstract><cop>Amsterdam</cop><pub>Elsevier Ltd</pub><pmid>18701278</pmid><doi>10.1016/j.bmcl.2008.07.078</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aldehyde-Lyases - analysis Aldehyde-Lyases - metabolism Anti-Bacterial Agents - metabolism Antibacterial agents Antibiotic Antibiotics. Antiinfectious agents. Antiparasitic agents Antimetabolites - metabolism Biological and medical sciences Coenzyme A Coenzyme A - metabolism Combinatorial Chemistry Techniques Cytochrome P-450 Enzyme System - analysis Cytochrome P-450 Enzyme System - metabolism Escherichia coli Escherichia coli - enzymology Escherichia coli - metabolism Fatty acid Medical sciences Molecular Structure Pantetheine - analogs & derivatives Pantetheine - chemical synthesis Pantetheine - chemistry Pantetheine - metabolism Pantothenamides Pharmacology. Drug treatments Structure-Activity Relationship Structure–activity relationships |
| title | Antibiotic evaluation and in vivo analysis of alkynyl Coenzyme A antimetabolites in Escherichia coli |
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