Analogues of peptide SMAP-29 with comparable antimicrobial potency and reduced cytotoxicity
SMAP-29 (sheep myeloid antimicrobial peptide-29) is a peptide with potent antibacterial properties. However, it is also highly cytotoxic both to human red blood cells (hRBCs) and human embryonic kidney (HEK) cells. In this study, some of the amino acids of SMAP-29 were changed in an attempt to reduc...
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| Veröffentlicht in: | International journal of antimicrobial agents 2011-05, Vol.37 (5), p.432-437 |
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| creator | Dawson, Raymond M Liu, Chun-Qiang |
| description | SMAP-29 (sheep myeloid antimicrobial peptide-29) is a peptide with potent antibacterial properties. However, it is also highly cytotoxic both to human red blood cells (hRBCs) and human embryonic kidney (HEK) cells. In this study, some of the amino acids of SMAP-29 were changed in an attempt to reduce haemolytic activity whilst maintaining high antibacterial efficacy. These analogues, plus other analogues described in the literature with potent antimicrobial activity against Gram-positive bacteria coupled with no or low haemolytic activity, were evaluated for their cytotoxicity (hRBCs and HEK cells) as well as antimicrobial efficacy against two Gram-positive (Bacillus anthracis and Bacillus globigii) and two Gram-negative bacteria (Escherichia coli and Burkholderia thailandensis). The analogues previously described in the literature were found to have low antibacterial and haemolytic activity. Two of the designed analogues had comparable antibacterial efficacy with SMAP-29 against B. anthracis but reduced haemolytic activity and therefore had a therapeutic index that was enhanced 2.3–2.6-fold over that of SMAP-29. |
| doi_str_mv | 10.1016/j.ijantimicag.2011.01.007 |
| format | Article |
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However, it is also highly cytotoxic both to human red blood cells (hRBCs) and human embryonic kidney (HEK) cells. In this study, some of the amino acids of SMAP-29 were changed in an attempt to reduce haemolytic activity whilst maintaining high antibacterial efficacy. These analogues, plus other analogues described in the literature with potent antimicrobial activity against Gram-positive bacteria coupled with no or low haemolytic activity, were evaluated for their cytotoxicity (hRBCs and HEK cells) as well as antimicrobial efficacy against two Gram-positive (Bacillus anthracis and Bacillus globigii) and two Gram-negative bacteria (Escherichia coli and Burkholderia thailandensis). The analogues previously described in the literature were found to have low antibacterial and haemolytic activity. Two of the designed analogues had comparable antibacterial efficacy with SMAP-29 against B. anthracis but reduced haemolytic activity and therefore had a therapeutic index that was enhanced 2.3–2.6-fold over that of SMAP-29.</description><identifier>ISSN: 0924-8579</identifier><identifier>EISSN: 1872-7913</identifier><identifier>DOI: 10.1016/j.ijantimicag.2011.01.007</identifier><identifier>PMID: 21377841</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>amino acids ; Anti-Bacterial Agents - pharmacology ; Anti-Bacterial Agents - toxicity ; anti-infective agents ; antibacterial properties ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Bacillus - drug effects ; Bacillus anthracis ; Bacillus subtilis ; Biological and medical sciences ; Blood Proteins - chemical synthesis ; Blood Proteins - pharmacology ; Blood Proteins - toxicity ; Burkholderia - drug effects ; Burkholderia thailandensis ; Cathelicidins ; Cytotoxicity ; Epithelial Cells - drug effects ; erythrocytes ; Erythrocytes - drug effects ; Escherichia coli ; Escherichia coli - drug effects ; Gram-negative bacteria ; Gram-positive bacteria ; Haemolysis ; hemolysis ; Humans ; Infectious Disease ; kidneys ; Medical sciences ; Microbial Sensitivity Tests ; Peptide ; Peptides - chemical synthesis ; Peptides - pharmacology ; Peptides - toxicity ; Pharmacology. Drug treatments ; sheep ; SMAP-29 ; Therapeutic index</subject><ispartof>International journal of antimicrobial agents, 2011-05, Vol.37 (5), p.432-437</ispartof><rights>2011</rights><rights>2015 INIST-CNRS</rights><rights>Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c485t-f507503f2f0ea3e79f2a55a9b6a0cec7032653bc297617d19cbb96186785920f3</citedby><cites>FETCH-LOGICAL-c485t-f507503f2f0ea3e79f2a55a9b6a0cec7032653bc297617d19cbb96186785920f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ijantimicag.2011.01.007$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24100107$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21377841$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dawson, Raymond M</creatorcontrib><creatorcontrib>Liu, Chun-Qiang</creatorcontrib><title>Analogues of peptide SMAP-29 with comparable antimicrobial potency and reduced cytotoxicity</title><title>International journal of antimicrobial agents</title><addtitle>Int J Antimicrob Agents</addtitle><description>SMAP-29 (sheep myeloid antimicrobial peptide-29) is a peptide with potent antibacterial properties. However, it is also highly cytotoxic both to human red blood cells (hRBCs) and human embryonic kidney (HEK) cells. In this study, some of the amino acids of SMAP-29 were changed in an attempt to reduce haemolytic activity whilst maintaining high antibacterial efficacy. These analogues, plus other analogues described in the literature with potent antimicrobial activity against Gram-positive bacteria coupled with no or low haemolytic activity, were evaluated for their cytotoxicity (hRBCs and HEK cells) as well as antimicrobial efficacy against two Gram-positive (Bacillus anthracis and Bacillus globigii) and two Gram-negative bacteria (Escherichia coli and Burkholderia thailandensis). The analogues previously described in the literature were found to have low antibacterial and haemolytic activity. Two of the designed analogues had comparable antibacterial efficacy with SMAP-29 against B. anthracis but reduced haemolytic activity and therefore had a therapeutic index that was enhanced 2.3–2.6-fold over that of SMAP-29.</description><subject>amino acids</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Anti-Bacterial Agents - toxicity</subject><subject>anti-infective agents</subject><subject>antibacterial properties</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Bacillus - drug effects</subject><subject>Bacillus anthracis</subject><subject>Bacillus subtilis</subject><subject>Biological and medical sciences</subject><subject>Blood Proteins - chemical synthesis</subject><subject>Blood Proteins - pharmacology</subject><subject>Blood Proteins - toxicity</subject><subject>Burkholderia - drug effects</subject><subject>Burkholderia thailandensis</subject><subject>Cathelicidins</subject><subject>Cytotoxicity</subject><subject>Epithelial Cells - drug effects</subject><subject>erythrocytes</subject><subject>Erythrocytes - drug effects</subject><subject>Escherichia coli</subject><subject>Escherichia coli - drug effects</subject><subject>Gram-negative bacteria</subject><subject>Gram-positive bacteria</subject><subject>Haemolysis</subject><subject>hemolysis</subject><subject>Humans</subject><subject>Infectious Disease</subject><subject>kidneys</subject><subject>Medical sciences</subject><subject>Microbial Sensitivity Tests</subject><subject>Peptide</subject><subject>Peptides - chemical synthesis</subject><subject>Peptides - pharmacology</subject><subject>Peptides - toxicity</subject><subject>Pharmacology. Drug treatments</subject><subject>sheep</subject><subject>SMAP-29</subject><subject>Therapeutic index</subject><issn>0924-8579</issn><issn>1872-7913</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkluL1DAUx4so7rj6FbQ-iE8dc2ma5kUYBm-wojDukw8hTU_G1LbpJqnab2-6M17wSTgQyPmd2_-cLHuK0RYjXL3otrZTY7SD1eq4JQjjLUqG-J1sg2tOCi4wvZttkCBlUTMuLrIHIXQIYUZLdj-7IJhyXpd4k33ejap3xxlC7kw-wRRtC_nh_e5jQUT-3cYvuXbDpLxqesjPRb1rrOrzyUUY9ZJ-29xDO2toc71EF90Pq21cHmb3jOoDPDq_l9n161ef9m-Lqw9v3u13V4UuaxYLwxBniBpiECgKXBiiGFOiqRTSoDmipGK00UTwCvMWC900osJ1xWsmCDL0Mnt-yjt5d5MmiXKwQUPfqxHcHGRd4RUUJJHiRKYRQvBg5OTtoPwiMZKrtLKTf0krV2klSoZ4in18rjI3A7S_I39pmYBnZ0AFrXrj1aht-MOVOC3gNtGTE2eUk-roE3N9SJVYcteE3ra5PxGQVPtmwcugbZIaWutBR9k6-18Nv_wni-7tmLD-KywQOjf7tPsgsQxEInlYr2U9Fpz6RKwi9CfMIbrc</recordid><startdate>20110501</startdate><enddate>20110501</enddate><creator>Dawson, Raymond M</creator><creator>Liu, Chun-Qiang</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>FBQ</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>20110501</creationdate><title>Analogues of peptide SMAP-29 with comparable antimicrobial potency and reduced cytotoxicity</title><author>Dawson, Raymond M ; Liu, Chun-Qiang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c485t-f507503f2f0ea3e79f2a55a9b6a0cec7032653bc297617d19cbb96186785920f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>amino acids</topic><topic>Anti-Bacterial Agents - pharmacology</topic><topic>Anti-Bacterial Agents - toxicity</topic><topic>anti-infective agents</topic><topic>antibacterial properties</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Bacillus - drug effects</topic><topic>Bacillus anthracis</topic><topic>Bacillus subtilis</topic><topic>Biological and medical sciences</topic><topic>Blood Proteins - chemical synthesis</topic><topic>Blood Proteins - pharmacology</topic><topic>Blood Proteins - toxicity</topic><topic>Burkholderia - drug effects</topic><topic>Burkholderia thailandensis</topic><topic>Cathelicidins</topic><topic>Cytotoxicity</topic><topic>Epithelial Cells - drug effects</topic><topic>erythrocytes</topic><topic>Erythrocytes - drug effects</topic><topic>Escherichia coli</topic><topic>Escherichia coli - drug effects</topic><topic>Gram-negative bacteria</topic><topic>Gram-positive bacteria</topic><topic>Haemolysis</topic><topic>hemolysis</topic><topic>Humans</topic><topic>Infectious Disease</topic><topic>kidneys</topic><topic>Medical sciences</topic><topic>Microbial Sensitivity Tests</topic><topic>Peptide</topic><topic>Peptides - chemical synthesis</topic><topic>Peptides - pharmacology</topic><topic>Peptides - toxicity</topic><topic>Pharmacology. Drug treatments</topic><topic>sheep</topic><topic>SMAP-29</topic><topic>Therapeutic index</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dawson, Raymond M</creatorcontrib><creatorcontrib>Liu, Chun-Qiang</creatorcontrib><collection>AGRIS</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>International journal of antimicrobial agents</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dawson, Raymond M</au><au>Liu, Chun-Qiang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Analogues of peptide SMAP-29 with comparable antimicrobial potency and reduced cytotoxicity</atitle><jtitle>International journal of antimicrobial agents</jtitle><addtitle>Int J Antimicrob Agents</addtitle><date>2011-05-01</date><risdate>2011</risdate><volume>37</volume><issue>5</issue><spage>432</spage><epage>437</epage><pages>432-437</pages><issn>0924-8579</issn><eissn>1872-7913</eissn><abstract>SMAP-29 (sheep myeloid antimicrobial peptide-29) is a peptide with potent antibacterial properties. However, it is also highly cytotoxic both to human red blood cells (hRBCs) and human embryonic kidney (HEK) cells. In this study, some of the amino acids of SMAP-29 were changed in an attempt to reduce haemolytic activity whilst maintaining high antibacterial efficacy. These analogues, plus other analogues described in the literature with potent antimicrobial activity against Gram-positive bacteria coupled with no or low haemolytic activity, were evaluated for their cytotoxicity (hRBCs and HEK cells) as well as antimicrobial efficacy against two Gram-positive (Bacillus anthracis and Bacillus globigii) and two Gram-negative bacteria (Escherichia coli and Burkholderia thailandensis). The analogues previously described in the literature were found to have low antibacterial and haemolytic activity. Two of the designed analogues had comparable antibacterial efficacy with SMAP-29 against B. anthracis but reduced haemolytic activity and therefore had a therapeutic index that was enhanced 2.3–2.6-fold over that of SMAP-29.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>21377841</pmid><doi>10.1016/j.ijantimicag.2011.01.007</doi><tpages>6</tpages></addata></record> |
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| subjects | amino acids Anti-Bacterial Agents - pharmacology Anti-Bacterial Agents - toxicity anti-infective agents antibacterial properties Antibiotics. Antiinfectious agents. Antiparasitic agents Bacillus - drug effects Bacillus anthracis Bacillus subtilis Biological and medical sciences Blood Proteins - chemical synthesis Blood Proteins - pharmacology Blood Proteins - toxicity Burkholderia - drug effects Burkholderia thailandensis Cathelicidins Cytotoxicity Epithelial Cells - drug effects erythrocytes Erythrocytes - drug effects Escherichia coli Escherichia coli - drug effects Gram-negative bacteria Gram-positive bacteria Haemolysis hemolysis Humans Infectious Disease kidneys Medical sciences Microbial Sensitivity Tests Peptide Peptides - chemical synthesis Peptides - pharmacology Peptides - toxicity Pharmacology. Drug treatments sheep SMAP-29 Therapeutic index |
| title | Analogues of peptide SMAP-29 with comparable antimicrobial potency and reduced cytotoxicity |
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