Conjugate of Enkephalin and Temporin Peptides as a Novel Therapeutic
Agent for Sepsis
Posted on 2018-12-10 - 19:37
Antimicrobial peptides (AMPs) exhibit
a wide spectrum of actions,
ranging from a direct bactericidal effect to multifunctional activities
as immune effector molecules. The aim of this study was to examine
the anti-inflammatory properties of a DAL-PEG-DK5 conjugate composed
of a lysine-rich derivative of amphibian temporin-1CEb (DK5) and dalargin
(DAL), the synthetic Leu-enkephalin analogue. Detailed study of the
endotoxin-neutralizing activity of the peptide revealed that DAL-PEG-DK5
interacts with LPS and the LPS binding protein (LBP). Moreover, DAL-PEG-DK5
prevented dimerization of TLR4 at the macrophage surface upon LPS
stimulation. This inhibited activation of the NF-κB signaling
pathway and markedly reduced pro-inflammatory cytokine production.
Finally, we showed that aggregation of DAL-PEG-DK5 into amyloid-like
structures induced by LPS neutralized the endotoxin proinflammatory
activity. Consequently, DAL-PEG-DK5 reduced morbidity and mortality in vivo, in a mouse model of endotoxin-induced septic shock.
Collectively, the data suggest that DAL-PEG-DK5 is a promising therapeutic
compound for sepsis.
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Golda, A.; Kosikowska-Adamus, P.; Babyak, O.; Lech, M.; Wysocka, M.; Lesner, A.; et al. (2018). Conjugate of Enkephalin and Temporin Peptides as a Novel Therapeutic
Agent for Sepsis. ACS Publications. Collection. https://doi.org/10.1021/acs.bioconjchem.8b00763
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AUTHORS (8)
AG
A. Golda
PK
P. Kosikowska-Adamus
OB
O. Babyak
ML
M. Lech
MW
M. Wysocka
AL
A. Lesner
JP
J. Potempa
JK
J. Koziel