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


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 - [Uniwersytet Jagielloński w Krakowie]
A. Golda,,
, Paulina Kosikowska-Adamus (FCh/DET/LBAN)
Paulina Kosikowska-Adamus,,
- Laboratory of Biochemical Analytics and Nanodiagnostics
, O. Babyak - [Uniwersytet Jagielloński w Krakowie]
O. Babyak,,
, M. Lech - [Uniwersytet Jagielloński w Krakowie]
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 - [Uniwersytet Jagielloński w Krakowie]
J. Potempa,,
, J. Koziel - [Uniwersytet Jagielloński w Krakowie]
J. Koziel,,
Journal seriesBioconjugate Chemistry, ISSN 1043-1802, (A 35 pkt)
Issue year2018
Publication size in sheets0.60
Languageen angielski
Score (nominal)40
ScoreMinisterial score = 35.0, ArticleFromJournal
Ministerial score (2013-2016) = 40.0, ArticleFromJournal
Publication indicators WoS Citations = 2.000; WoS Impact Factor: 2017 = 4.485 (2) - 2017=4.416 (5); Scopus Citations = 5.000
Citation count*5 (2020-08-01)
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* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.
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