Peptide/β-Peptoid Hybrids with Ultrashort PEG-Like Moieties: Effects on Hydrophobicity, Antibacterial Activity and Hemolytic Properties
| Autor: | Magdalena Tomczak, Ilona Domraceva, Osvalds Pugovics, Chirag Mudaliar, Stavroula Louka, Weronika Wygoda, Agrita Kreicberga, Fredrik Björkling, Dorota Żabicka, Nicki Frederiksen, Henrik Franzyk |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Acinetobacter baumannii
0301 basic medicine QH301-705.5 Cell Survival Peptidomimetic Stereochemistry 030106 microbiology Peptide Microbial Sensitivity Tests Article Catalysis Polyethylene Glycols Inorganic Chemistry Peptoids 03 medical and health sciences chemistry.chemical_compound antibacterial activity Drug Resistance Bacterial PEG ratio Escherichia coli medicine Humans HepG2 cell viability Biology (General) Physical and Theoretical Chemistry QD1-999 Molecular Biology Spectroscopy hydrophobicity chemistry.chemical_classification Molecular Structure Chemistry Organic Chemistry Peptoid Hep G2 Cells General Medicine medicine.disease Hemolysis Anti-Bacterial Agents Computer Science Applications Amino acid 030104 developmental biology peptidomimetics PEGylation ultrashort PEG-like moieties hemolysis Antibacterial activity Hydrophobic and Hydrophilic Interactions |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 13 International Journal of Molecular Sciences, Vol 22, Iss 7041, p 7041 (2021) Frederiksen, N, Louka, S, Mudaliar, C, Domraceva, I, Kreicberga, A, Pugovics, O, Żabicka, D, Tomczak, M, Wygoda, W, Björkling, F & Franzyk, H 2021, ' Peptide/β-Peptoid Hybrids with Ultrashort PEG-Like Moieties : Effects on Hydrophobicity, Antibacterial Activity and Hemolytic Properties ', International Journal of Molecular Sciences, vol. 22, no. 13, 7041 . https://doi.org/10.3390/ijms22137041 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms22137041 |
| Popis: | 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 Escherichia coli and Acinetobacter baumannii (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 IC50 values of ~1280 µg/mL) as compared to most other analogues and the parent peptidomimetic (IC50 values in the range 330–800 µg/mL). |
| Databáze: | OpenAIRE |
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