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

Abstract

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 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.
Author A. Golda
A. Golda,,
-
, Paulina Kosikowska-Adamus (FCh / DMB / LBA)
Paulina Kosikowska-Adamus,,
- Laboratory of Biochemical Analytics
, O. Babyak
O. Babyak,,
-
, M. Lech
M. Lech,,
-
, Magdalena Wysocka (FCh / DBCh / LMCh)
Magdalena Wysocka,,
- Laboratory of Medical Chemistry
, Adam Lesner (FCh / DET / LBAN)
Adam Lesner,,
- Laboratory of Biochemical Analytics and Nanodiagnostics
, J. Potempa
J. Potempa,,
-
, J. Koziel
J. Koziel,,
-
Journal seriesBioconjugate Chemistry, ISSN 1043-1802, (A 35 pkt)
Issue year2018
Vol29
No12
Pages4127-4139
Publication size in sheets0.6
DOIDOI:10.1021/acs.bioconjchem.8b00763
URL http://dx.doi.org/10.1021/acs.bioconjchem.8b00763
Languageen angielski
Score (nominal)40
ScoreMinisterial score = 35.0, ArticleFromJournal
Ministerial score (2013-2016) = 40.0, ArticleFromJournal
Publication indicators WoS Citations = 0; WoS Impact Factor: 2017 = 4.485 (2) - 2017=4.416 (5)
Citation count*
Cite
Share Share

Get link to the record


* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.
Back