Antifungal properties of peptidomimetics with an arginine-[β-(2,5,7-tri-tert-butylindol-3-yl)alanine]-arginine motif against Saccharomyces cerevisiae and Zygosaccharomyces bailii
Due to increased occurrence of infections and food spoilage caused by yeast, there is an unmet need for new antifungal agents. The arginine-β-(2,5,7-tri-tert-butylindol-3-yl) alanine-arginine (R-Tbt-R) motif was previously proved useful in the design of an antifungal tripeptide. Here, an array of pe...
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| description | Due to increased occurrence of infections and food spoilage caused by yeast, there is an unmet need for new antifungal agents. The arginine-β-(2,5,7-tri-tert-butylindol-3-yl) alanine-arginine (R-Tbt-R) motif was previously proved useful in the design of an antifungal tripeptide. Here, an array of peptidomimetics based on this motif was investigated for antifungal and hemolytic activity. The five most promising modified tetrapeptide analogues (6 and 9–12) contain an additional C-terminal hydrophobic residue, and these were found to exhibit antifungal activity against Saccharomyces cerevisiae (MIC 6 and 12 μg mL−1) and Zygosaccharomyces bailii (MIC 6–25 μg mL−1). Four compounds (6 and 9–11), had limited hemolytic activity ( |
| doi_str_mv | 10.1093/femsyr/fov011 |
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Peptidomimetics based on the Arg-Trp-Arg motif are antifungal agents.</description><identifier>ISSN: 1567-1356</identifier><identifier>EISSN: 1567-1364</identifier><identifier>DOI: 10.1093/femsyr/fov011</identifier><identifier>PMID: 25761917</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Alanine ; Antifungal activity ; Antifungal agents ; Antifungal Agents - chemistry ; Antifungal Agents - pharmacology ; Antifungal Agents - toxicity ; Arginine ; Biodegradation ; Candida - drug effects ; Clonal deletion ; Deletion mutant ; Food spoilage ; Hemolysis - drug effects ; Hydrophobicity ; Microbial Sensitivity Tests ; Microbial Viability - drug effects ; Minimum inhibitory concentration ; Peptidomimetics ; Peptidomimetics - chemistry ; Peptidomimetics - pharmacology ; Peptidomimetics - toxicity ; Preservatives ; Saccharomyces cerevisiae ; Saccharomyces cerevisiae - drug effects ; Sphingolipids ; Toxicity ; Yeast ; Zygosaccharomyces - drug effects ; Zygosaccharomyces bailii</subject><ispartof>FEMS yeast research, 2015-05, Vol.15 (3)</ispartof><rights>FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 2015</rights><rights>FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.</rights><rights>FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c463t-3b00f321550d18f8a2ca98bfb7e79cb382b76be86d9178631364cdeac7079e2c3</citedby><cites>FETCH-LOGICAL-c463t-3b00f321550d18f8a2ca98bfb7e79cb382b76be86d9178631364cdeac7079e2c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1598,27901,27902</link.rule.ids><linktorsrc>$$Uhttps://dx.doi.org/10.1093/femsyr/fov011$$EView_record_in_Oxford_University_Press$$FView_record_in_$$GOxford_University_Press</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25761917$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Larsen, Camilla Eggert</creatorcontrib><creatorcontrib>Larsen, Camilla Josephine</creatorcontrib><creatorcontrib>Franzyk, Henrik</creatorcontrib><creatorcontrib>Regenberg, Birgitte</creatorcontrib><title>Antifungal properties of peptidomimetics with an arginine-[β-(2,5,7-tri-tert-butylindol-3-yl)alanine]-arginine motif against Saccharomyces cerevisiae and Zygosaccharomyces bailii</title><title>FEMS yeast research</title><addtitle>FEMS Yeast Res</addtitle><description>Due to increased occurrence of infections and food spoilage caused by yeast, there is an unmet need for new antifungal agents. The arginine-β-(2,5,7-tri-tert-butylindol-3-yl) alanine-arginine (R-Tbt-R) motif was previously proved useful in the design of an antifungal tripeptide. Here, an array of peptidomimetics based on this motif was investigated for antifungal and hemolytic activity. The five most promising modified tetrapeptide analogues (6 and 9–12) contain an additional C-terminal hydrophobic residue, and these were found to exhibit antifungal activity against Saccharomyces cerevisiae (MIC 6 and 12 μg mL−1) and Zygosaccharomyces bailii (MIC 6–25 μg mL−1). Four compounds (6 and 9–11), had limited hemolytic activity (<10% hemolysis at 8 × MIC). Determination of their killing kinetics revealed that compound 9 displayed fungicidal effect. Testing against cells from an S. cerevisiae deletion mutant library indicated that interaction with yeast-specific fungal sphingolipids, most likely constitutes a crucial step in the mode of action. Interestingly, a lack of activity of peptidomimetics 6 and 9–11 towards Candida spp. was shown to be due to degradation or sequestering by the yeast. Due to their ultrashort nature, antifungal activity and low toxicity, the four compounds may have potential as leads for novel preservatives.
Peptidomimetics based on the Arg-Trp-Arg motif are antifungal agents.</description><subject>Alanine</subject><subject>Antifungal activity</subject><subject>Antifungal agents</subject><subject>Antifungal Agents - chemistry</subject><subject>Antifungal Agents - pharmacology</subject><subject>Antifungal Agents - toxicity</subject><subject>Arginine</subject><subject>Biodegradation</subject><subject>Candida - drug effects</subject><subject>Clonal deletion</subject><subject>Deletion mutant</subject><subject>Food spoilage</subject><subject>Hemolysis - drug effects</subject><subject>Hydrophobicity</subject><subject>Microbial Sensitivity Tests</subject><subject>Microbial Viability - drug effects</subject><subject>Minimum inhibitory concentration</subject><subject>Peptidomimetics</subject><subject>Peptidomimetics - chemistry</subject><subject>Peptidomimetics - pharmacology</subject><subject>Peptidomimetics - toxicity</subject><subject>Preservatives</subject><subject>Saccharomyces cerevisiae</subject><subject>Saccharomyces cerevisiae - drug effects</subject><subject>Sphingolipids</subject><subject>Toxicity</subject><subject>Yeast</subject><subject>Zygosaccharomyces - drug effects</subject><subject>Zygosaccharomyces bailii</subject><issn>1567-1356</issn><issn>1567-1364</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkctq3jAUhEVpaC7tstsi6CaFKNHltyUvQ-glEOgi7aalGEk--qNgW64kp_i1mvfoM1U_TgJddXXO4psZmEHoNaOnjDbizMGQlnjmwh1l7Bk6YFUtCRP15vnTX9X76DClW0qZpFS9QPu8kjVrmDxA9-dj9m4et7rHUwwTxOwh4eDwBFP2XRj8ANnbhH_5fIP1iHXc-tGPQL7_-U2O-Ul1IkmOnuQiJWbOS-_HLvREkKV_p3u9Y3-QRxUeQsnDeqv9mDK-1tbe6BiGxZZUCxHufPIaSlCHvy3bkP4BjPa99y_RntN9glcP9wh9_fD-y8UncvX54-XF-RWxm1pkIgylTnBWVbRjyinNrW6UcUaCbKwRihtZG1B1V5pQtdiVZjvQVlLZALfiCL1dfUsxP2dIub0NcxxLZMuF2HClmooXiqyUjSGlCK6doh90XFpG291E7TpRu05U-DcPrrMZoHuiHzcpwPEKhHn6j9df2yyhrg</recordid><startdate>20150501</startdate><enddate>20150501</enddate><creator>Larsen, Camilla Eggert</creator><creator>Larsen, Camilla Josephine</creator><creator>Franzyk, Henrik</creator><creator>Regenberg, Birgitte</creator><general>Oxford University 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>88E</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>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20150501</creationdate><title>Antifungal properties of peptidomimetics with an arginine-[β-(2,5,7-tri-tert-butylindol-3-yl)alanine]-arginine motif against Saccharomyces cerevisiae and Zygosaccharomyces bailii</title><author>Larsen, Camilla Eggert ; Larsen, Camilla Josephine ; Franzyk, Henrik ; Regenberg, Birgitte</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c463t-3b00f321550d18f8a2ca98bfb7e79cb382b76be86d9178631364cdeac7079e2c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Alanine</topic><topic>Antifungal activity</topic><topic>Antifungal agents</topic><topic>Antifungal Agents - chemistry</topic><topic>Antifungal Agents - pharmacology</topic><topic>Antifungal Agents - toxicity</topic><topic>Arginine</topic><topic>Biodegradation</topic><topic>Candida - drug effects</topic><topic>Clonal deletion</topic><topic>Deletion mutant</topic><topic>Food spoilage</topic><topic>Hemolysis - drug effects</topic><topic>Hydrophobicity</topic><topic>Microbial Sensitivity Tests</topic><topic>Microbial Viability - drug effects</topic><topic>Minimum inhibitory concentration</topic><topic>Peptidomimetics</topic><topic>Peptidomimetics - chemistry</topic><topic>Peptidomimetics - pharmacology</topic><topic>Peptidomimetics - toxicity</topic><topic>Preservatives</topic><topic>Saccharomyces cerevisiae</topic><topic>Saccharomyces cerevisiae - drug effects</topic><topic>Sphingolipids</topic><topic>Toxicity</topic><topic>Yeast</topic><topic>Zygosaccharomyces - drug effects</topic><topic>Zygosaccharomyces bailii</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Larsen, Camilla Eggert</creatorcontrib><creatorcontrib>Larsen, Camilla Josephine</creatorcontrib><creatorcontrib>Franzyk, Henrik</creatorcontrib><creatorcontrib>Regenberg, Birgitte</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>Medical Database (Alumni Edition)</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</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>Medical Database</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><jtitle>FEMS yeast research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Larsen, Camilla Eggert</au><au>Larsen, Camilla Josephine</au><au>Franzyk, Henrik</au><au>Regenberg, Birgitte</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antifungal properties of peptidomimetics with an arginine-[β-(2,5,7-tri-tert-butylindol-3-yl)alanine]-arginine motif against Saccharomyces cerevisiae and Zygosaccharomyces bailii</atitle><jtitle>FEMS yeast research</jtitle><addtitle>FEMS Yeast Res</addtitle><date>2015-05-01</date><risdate>2015</risdate><volume>15</volume><issue>3</issue><issn>1567-1356</issn><eissn>1567-1364</eissn><abstract>Due to increased occurrence of infections and food spoilage caused by yeast, there is an unmet need for new antifungal agents. The arginine-β-(2,5,7-tri-tert-butylindol-3-yl) alanine-arginine (R-Tbt-R) motif was previously proved useful in the design of an antifungal tripeptide. Here, an array of peptidomimetics based on this motif was investigated for antifungal and hemolytic activity. The five most promising modified tetrapeptide analogues (6 and 9–12) contain an additional C-terminal hydrophobic residue, and these were found to exhibit antifungal activity against Saccharomyces cerevisiae (MIC 6 and 12 μg mL−1) and Zygosaccharomyces bailii (MIC 6–25 μg mL−1). Four compounds (6 and 9–11), had limited hemolytic activity (<10% hemolysis at 8 × MIC). Determination of their killing kinetics revealed that compound 9 displayed fungicidal effect. Testing against cells from an S. cerevisiae deletion mutant library indicated that interaction with yeast-specific fungal sphingolipids, most likely constitutes a crucial step in the mode of action. Interestingly, a lack of activity of peptidomimetics 6 and 9–11 towards Candida spp. was shown to be due to degradation or sequestering by the yeast. Due to their ultrashort nature, antifungal activity and low toxicity, the four compounds may have potential as leads for novel preservatives.
Peptidomimetics based on the Arg-Trp-Arg motif are antifungal agents.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>25761917</pmid><doi>10.1093/femsyr/fov011</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Alanine Antifungal activity Antifungal agents Antifungal Agents - chemistry Antifungal Agents - pharmacology Antifungal Agents - toxicity Arginine Biodegradation Candida - drug effects Clonal deletion Deletion mutant Food spoilage Hemolysis - drug effects Hydrophobicity Microbial Sensitivity Tests Microbial Viability - drug effects Minimum inhibitory concentration Peptidomimetics Peptidomimetics - chemistry Peptidomimetics - pharmacology Peptidomimetics - toxicity Preservatives Saccharomyces cerevisiae Saccharomyces cerevisiae - drug effects Sphingolipids Toxicity Yeast Zygosaccharomyces - drug effects Zygosaccharomyces bailii |
| title | Antifungal properties of peptidomimetics with an arginine-[β-(2,5,7-tri-tert-butylindol-3-yl)alanine]-arginine motif against Saccharomyces cerevisiae and Zygosaccharomyces bailii |
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