Conjugate of Enkephalin and Temporin Peptides as a Novel Therapeutic Agent for Sepsis

Golda, A.; Kosikowska-Adamus, P.; Babyak, O.; Lech, M.; Wysocka, M.; Lesner, A.; Potempa, J. und Koziel, J. (2018): Conjugate of Enkephalin and Temporin Peptides as a Novel Therapeutic Agent for Sepsis. In: Bioconjugate Chemistry, Bd. 29, Nr. 12: S. 4127-4139

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 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-kappa 13 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-DKS is a promising therapeutic compound for sepsis.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1043-1802
• Sprache: Englisch