Peptide/β-Peptoid Hybrids with Ultrashort PEG-Like Moieties: Effects on Hydrophobicity, Antibacterial Activity and Hemolytic Properties
PEGylation of antimicrobial peptides as a shielding tool that increases stability toward proteolytic degradation typically leads to concomitant loss of activity, whereas incorporation of ultrashort PEG-like amino acids (sPEGs) remains essentially unexplored. Here, modification of a peptide/β-peptoid...
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MDPI AG
2021-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/13/7041 |
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| author | Nicki Frederiksen Stavroula Louka Chirag Mudaliar Ilona Domraceva Agrita Kreicberga Osvalds Pugovics Dorota Żabicka Magdalena Tomczak Weronika Wygoda Fredrik Björkling Henrik Franzyk |
| author_facet | Nicki Frederiksen Stavroula Louka Chirag Mudaliar Ilona Domraceva Agrita Kreicberga Osvalds Pugovics Dorota Żabicka Magdalena Tomczak Weronika Wygoda Fredrik Björkling Henrik Franzyk |
| author_sort | Nicki Frederiksen |
| collection | DOAJ |
| description | PEGylation of antimicrobial peptides as a shielding tool that increases stability toward proteolytic degradation typically leads to concomitant loss of activity, whereas incorporation of ultrashort PEG-like amino acids (sPEGs) remains essentially unexplored. Here, modification of a peptide/β-peptoid hybrid with sPEGs was examined with respect to influence on hydrophobicity, antibacterial activity and effect on viability of mammalian cells for a set of 18 oligomers. Intriguingly, the degree of sPEG modification did not significantly affect hydrophobicity as measured by retention in reverse-phase HPLC. Antibacterial activity against both wild-type and drug-resistant strains of <i>Escherichia coli</i> and <i>Acinetobacter baumannii</i> (both Gram-negative pathogens) was retained or slightly improved (MICs in the range 2–16 µg/mL equal to 0.7–5.2 µM). All compounds in the series exhibited less than 10% hemolysis at 400 µg/mL. While the number of sPEG moieties appeared not to be clearly correlated with hemolytic activity, a trend toward slightly increased hemolytic activity was observed for analogues displaying the longest sPEGs. In contrast, within a subseries the viability of HepG2 liver cells was least affected by analogues displaying the longer sPEGs (with IC<sub>50</sub> values of ~1280 µg/mL) as compared to most other analogues and the parent peptidomimetic (IC<sub>50</sub> values in the range 330–800 µg/mL). |
| first_indexed | 2024-03-10T09:57:14Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T09:57:14Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f3dbbe7ffcb64906a3c6628daa94a7182023-11-22T02:19:10ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012213704110.3390/ijms22137041Peptide/β-Peptoid Hybrids with Ultrashort PEG-Like Moieties: Effects on Hydrophobicity, Antibacterial Activity and Hemolytic PropertiesNicki Frederiksen0Stavroula Louka1Chirag Mudaliar2Ilona Domraceva3Agrita Kreicberga4Osvalds Pugovics5Dorota Żabicka6Magdalena Tomczak7Weronika Wygoda8Fredrik Björkling9Henrik Franzyk10Center for Peptide-Based Antibiotics, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100 Copenhagen, DenmarkCenter for Peptide-Based Antibiotics, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100 Copenhagen, DenmarkCenter for Peptide-Based Antibiotics, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100 Copenhagen, DenmarkLatvian Institute of Organic Synthesis, Aizkraukles 21, 1006 Riga, LatviaLatvian Institute of Organic Synthesis, Aizkraukles 21, 1006 Riga, LatviaLatvian Institute of Organic Synthesis, Aizkraukles 21, 1006 Riga, LatviaDepartment of Epidemiology and Clinical Microbiology, National Medicines Institute, ul. Chełmska 30/34, 00-725 Warsaw, PolandDepartment of Epidemiology and Clinical Microbiology, National Medicines Institute, ul. Chełmska 30/34, 00-725 Warsaw, PolandDepartment of Epidemiology and Clinical Microbiology, National Medicines Institute, ul. Chełmska 30/34, 00-725 Warsaw, PolandCenter for Peptide-Based Antibiotics, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100 Copenhagen, DenmarkCenter for Peptide-Based Antibiotics, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100 Copenhagen, DenmarkPEGylation of antimicrobial peptides as a shielding tool that increases stability toward proteolytic degradation typically leads to concomitant loss of activity, whereas incorporation of ultrashort PEG-like amino acids (sPEGs) remains essentially unexplored. Here, modification of a peptide/β-peptoid hybrid with sPEGs was examined with respect to influence on hydrophobicity, antibacterial activity and effect on viability of mammalian cells for a set of 18 oligomers. Intriguingly, the degree of sPEG modification did not significantly affect hydrophobicity as measured by retention in reverse-phase HPLC. Antibacterial activity against both wild-type and drug-resistant strains of <i>Escherichia coli</i> and <i>Acinetobacter baumannii</i> (both Gram-negative pathogens) was retained or slightly improved (MICs in the range 2–16 µg/mL equal to 0.7–5.2 µM). All compounds in the series exhibited less than 10% hemolysis at 400 µg/mL. While the number of sPEG moieties appeared not to be clearly correlated with hemolytic activity, a trend toward slightly increased hemolytic activity was observed for analogues displaying the longest sPEGs. In contrast, within a subseries the viability of HepG2 liver cells was least affected by analogues displaying the longer sPEGs (with IC<sub>50</sub> values of ~1280 µg/mL) as compared to most other analogues and the parent peptidomimetic (IC<sub>50</sub> values in the range 330–800 µg/mL).https://www.mdpi.com/1422-0067/22/13/7041peptidomimeticsultrashort PEG-like moietieshydrophobicityantibacterial activityhemolysisHepG2 cell viability |
| spellingShingle | Nicki Frederiksen Stavroula Louka Chirag Mudaliar Ilona Domraceva Agrita Kreicberga Osvalds Pugovics Dorota Żabicka Magdalena Tomczak Weronika Wygoda Fredrik Björkling Henrik Franzyk Peptide/β-Peptoid Hybrids with Ultrashort PEG-Like Moieties: Effects on Hydrophobicity, Antibacterial Activity and Hemolytic Properties International Journal of Molecular Sciences peptidomimetics ultrashort PEG-like moieties hydrophobicity antibacterial activity hemolysis HepG2 cell viability |
| title | Peptide/β-Peptoid Hybrids with Ultrashort PEG-Like Moieties: Effects on Hydrophobicity, Antibacterial Activity and Hemolytic Properties |
| title_full | Peptide/β-Peptoid Hybrids with Ultrashort PEG-Like Moieties: Effects on Hydrophobicity, Antibacterial Activity and Hemolytic Properties |
| title_fullStr | Peptide/β-Peptoid Hybrids with Ultrashort PEG-Like Moieties: Effects on Hydrophobicity, Antibacterial Activity and Hemolytic Properties |
| title_full_unstemmed | Peptide/β-Peptoid Hybrids with Ultrashort PEG-Like Moieties: Effects on Hydrophobicity, Antibacterial Activity and Hemolytic Properties |
| title_short | Peptide/β-Peptoid Hybrids with Ultrashort PEG-Like Moieties: Effects on Hydrophobicity, Antibacterial Activity and Hemolytic Properties |
| title_sort | peptide β peptoid hybrids with ultrashort peg like moieties effects on hydrophobicity antibacterial activity and hemolytic properties |
| topic | peptidomimetics ultrashort PEG-like moieties hydrophobicity antibacterial activity hemolysis HepG2 cell viability |
| url | https://www.mdpi.com/1422-0067/22/13/7041 |
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