TY - JOUR

T1 - Peptide/β-Peptoid Hybrids with Ultrashort PEG-Like Moieties

T2 - Effects on Hydrophobicity, Antibacterial Activity and Hemolytic Properties

AU - Frederiksen, Nicki

AU - Louka, Stavroula

AU - Mudaliar, Chirag

AU - Domraceva, Ilona

AU - Kreicberga, Agrita

AU - Pugovics, Osvalds

AU - Żabicka, Dorota

AU - Tomczak, Magdalena

AU - Wygoda, Weronika

AU - Björkling, Fredrik

AU - Franzyk, Henrik

PY - 2021

Y1 - 2021

N2 - 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).

AB - 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).

U2 - 10.3390/ijms22137041

DO - 10.3390/ijms22137041

M3 - Journal article

C2 - 34208826

VL - 22

JO - International Journal of Molecular Sciences (CD-ROM)

JF - International Journal of Molecular Sciences (CD-ROM)

SN - 1424-6783

IS - 13

M1 - 7041

ER -