What Goes around Comes around-A Comparative Study of the Influence of Chemical Modifications on the Antimicrobial Properties of Small Cyclic Peptides
Tryptophan and arginine-rich cyclic hexapeptides of the type cyclo-RRRWFW combine high antibacterial activity with rapid cell killing kinetics, but show low toxicity in human cell lines. The peptides fulfil the structural requirements for membrane interaction such as high amphipathicity and cationic...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2013-09-01
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| Series: | Pharmaceuticals |
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| Online Access: | http://www.mdpi.com/1424-8247/6/9/1130 |
| _version_ | 1811225812872986624 |
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| author | Margitta Dathe Marina Rautenbach Igor V. Komarov Heike Nikolenko Kathi Scheinpflug |
| author_facet | Margitta Dathe Marina Rautenbach Igor V. Komarov Heike Nikolenko Kathi Scheinpflug |
| author_sort | Margitta Dathe |
| collection | DOAJ |
| description | Tryptophan and arginine-rich cyclic hexapeptides of the type cyclo-RRRWFW combine high antibacterial activity with rapid cell killing kinetics, but show low toxicity in human cell lines. The peptides fulfil the structural requirements for membrane interaction such as high amphipathicity and cationic charge, but membrane permeabilisation, which is the most common mode of action of antimicrobial peptides (AMPs), could not be observed. Our current studies focus on elucidating a putative membrane translocation mechanism whereupon the peptides might interfere with intracellular processes. These investigations require particular analytical tools: fluorescent analogues and peptides bearing appropriate reactive groups were synthesized and characterized in order to be used in confocal laser scanning microscopy and HPLC analysis. We found that minimal changes in both the cationic and hydrophobic domain of the peptides in most cases led to significant reduction of antimicrobial activity and/or changes in the mode of action. However, we were able to identify two modified peptides which exhibited properties similar to those of the cyclic parent hexapeptide and are suitable for subsequent studies on membrane translocation and uptake into bacterial cells. |
| first_indexed | 2024-04-12T09:14:46Z |
| format | Article |
| id | doaj.art-43f3447b81bc4013928f73436100e465 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-04-12T09:14:46Z |
| publishDate | 2013-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-43f3447b81bc4013928f73436100e4652022-12-22T03:38:53ZengMDPI AGPharmaceuticals1424-82472013-09-01691130114410.3390/ph6091130What Goes around Comes around-A Comparative Study of the Influence of Chemical Modifications on the Antimicrobial Properties of Small Cyclic PeptidesMargitta DatheMarina RautenbachIgor V. KomarovHeike NikolenkoKathi ScheinpflugTryptophan and arginine-rich cyclic hexapeptides of the type cyclo-RRRWFW combine high antibacterial activity with rapid cell killing kinetics, but show low toxicity in human cell lines. The peptides fulfil the structural requirements for membrane interaction such as high amphipathicity and cationic charge, but membrane permeabilisation, which is the most common mode of action of antimicrobial peptides (AMPs), could not be observed. Our current studies focus on elucidating a putative membrane translocation mechanism whereupon the peptides might interfere with intracellular processes. These investigations require particular analytical tools: fluorescent analogues and peptides bearing appropriate reactive groups were synthesized and characterized in order to be used in confocal laser scanning microscopy and HPLC analysis. We found that minimal changes in both the cationic and hydrophobic domain of the peptides in most cases led to significant reduction of antimicrobial activity and/or changes in the mode of action. However, we were able to identify two modified peptides which exhibited properties similar to those of the cyclic parent hexapeptide and are suitable for subsequent studies on membrane translocation and uptake into bacterial cells.http://www.mdpi.com/1424-8247/6/9/1130cyclic hexapeptidesantimicrobial activitymode of actionpermeabilisationchemical modification |
| spellingShingle | Margitta Dathe Marina Rautenbach Igor V. Komarov Heike Nikolenko Kathi Scheinpflug What Goes around Comes around-A Comparative Study of the Influence of Chemical Modifications on the Antimicrobial Properties of Small Cyclic Peptides Pharmaceuticals cyclic hexapeptides antimicrobial activity mode of action permeabilisation chemical modification |
| title | What Goes around Comes around-A Comparative Study of the Influence of Chemical Modifications on the Antimicrobial Properties of Small Cyclic Peptides |
| title_full | What Goes around Comes around-A Comparative Study of the Influence of Chemical Modifications on the Antimicrobial Properties of Small Cyclic Peptides |
| title_fullStr | What Goes around Comes around-A Comparative Study of the Influence of Chemical Modifications on the Antimicrobial Properties of Small Cyclic Peptides |
| title_full_unstemmed | What Goes around Comes around-A Comparative Study of the Influence of Chemical Modifications on the Antimicrobial Properties of Small Cyclic Peptides |
| title_short | What Goes around Comes around-A Comparative Study of the Influence of Chemical Modifications on the Antimicrobial Properties of Small Cyclic Peptides |
| title_sort | what goes around comes around a comparative study of the influence of chemical modifications on the antimicrobial properties of small cyclic peptides |
| topic | cyclic hexapeptides antimicrobial activity mode of action permeabilisation chemical modification |
| url | http://www.mdpi.com/1424-8247/6/9/1130 |
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