posted on 2022-12-13, 11:43authored byHongyan Yang, Lan Wang, Libo Yuan, Heng Du, Boyuan Pan, Kui Lu
A series of hybrid peptides were designed by connecting
an antimicrobial
peptide Ce(1–8) with a lipopolysaccharide (LPS)-targeting peptide
Lf(28–34) via different linkers. Antimicrobial experimental
results indicated that linkers play an essential role in the anti-Gram-negative
bacterial activity of the hybrid peptides. Among these hybrid peptides,
peptide CL5 with dipeptide rigid linker LP exhibited excellent activity
and selectivity against Gram-negative bacteria. The minimum inhibitory
concentrations of CL5 against the tested Gram-negative bacteria were
4–32 μM, while the toxicity toward HEK-293 cells was
relatively low. It was found that the interactions of the peptides
with LPS were crucial for peptide activity against Gram-negative bacteria.
Antimicrobial mechanistic studies showed that peptide CL5 contributed
to the death of Gram-negative bacterial cells by disrupting the integrity
of the bacterial membranes. This study revealed the importance of
linker selection in the design of hybrid peptides and provides the
basis for the further development of antimicrobial peptides.