Peptide/β-Peptoid Hybrids with Ultrashort PEG-Like Moieties: Effects on Hydrophobicity, Antibacterial Activity and Hemolytic Properties.

Autor: Frederiksen N; Center for Peptide-Based Antibiotics, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark., Louka S; Center for Peptide-Based Antibiotics, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark., Mudaliar C; Center for Peptide-Based Antibiotics, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark., Domraceva I; Latvian Institute of Organic Synthesis, Aizkraukles 21, 1006 Riga, Latvia., Kreicberga A; Latvian Institute of Organic Synthesis, Aizkraukles 21, 1006 Riga, Latvia., Pugovics O; Latvian Institute of Organic Synthesis, Aizkraukles 21, 1006 Riga, Latvia., Żabicka D; Department of Epidemiology and Clinical Microbiology, National Medicines Institute, ul. Chełmska 30/34, 00-725 Warsaw, Poland., Tomczak M; Department of Epidemiology and Clinical Microbiology, National Medicines Institute, ul. Chełmska 30/34, 00-725 Warsaw, Poland., Wygoda W; Department of Epidemiology and Clinical Microbiology, National Medicines Institute, ul. Chełmska 30/34, 00-725 Warsaw, Poland., Björkling F; Center for Peptide-Based Antibiotics, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark., Franzyk H; Center for Peptide-Based Antibiotics, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2021 Jun 30; Vol. 22 (13). Date of Electronic Publication: 2021 Jun 30.
DOI: 10.3390/ijms22137041
Abstrakt: 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 IC 50 values of ~1280 µg/mL) as compared to most other analogues and the parent peptidomimetic (IC 50 values in the range 330-800 µg/mL).
Databáze: MEDLINE
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