Conjugate of enkephalin and temporin peptides as a novel therapeutic agent for sepsis
A. Golda , Paulina Kosikowska-Adamus , O. Babyak , M. Lech , Magdalena Wysocka , Adam Lesner , J. Potempa , J. Koziel
AbstractAntimicrobial 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 Leuenkephalin 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.
|Journal series||Bioconjugate Chemistry, ISSN 1043-1802, (A 35 pkt)|
|Publication size in sheets||0.60|
|Score|| = 35.0, ArticleFromJournal|
= 40.0, ArticleFromJournal
|Publication indicators||= 2.000; : 2017 = 4.485 (2) - 2017=4.416 (5); = 5.000|
|Citation count*||5 (2020-08-01)|
* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.