Carbamylated LL-37 as a modulator of the immune response

Research output: Contribution to journalArticlepeer-review


  • Catalin Koro
  • Annelie Hellvard
  • Nicolas Delaleu
  • Veronika Binder
  • Carsten Scavenius
  • Brith Bergum
  • Izabela Główczyk
  • Helen Roberts
  • Maria Rapala-Kozik
  • Kinga Klaga
  • Jan Enghild
  • Piotr Mydel

Colleges, School and Institutes

External organisations

  • epartment of Clinical Science, University of Bergen


Carbamylation of lysine residues and protein N-termini is a ubiquitous, non-enzymatic post-translational modification. Carbamylation at sites of inflammation is due to cyanate formation during the neutrophil oxidative burst and may target lysine residues within the antimicrobial peptide LL-37. The bactericidal and immunomodulatory properties of LL-37 depend on its secondary structure and cationic nature, which are conferred by arginine and lysine residues. Therefore, carbamylation may affect the biological functions of LL-37. The present study examined the kinetics and pattern of LL-37 carbamylation to investigate how this modification affects the bactericidal, cytotoxic, and immunomodulatory function of the peptide. The results indicated that LL-37 undergoes rapid modification in the presence of physiological concentrations of cyanate, yielding a spectrum of diverse carbamylated peptides. Mass spectrometry analyses revealed that the N-terminal amino group of Leu-1 was highly reactive and was modified almost instantly by cyanate to generate the predominant form of the modified peptide, named LL37C1. This was followed by the sequential carbamylation of Lys-8, Lys-12, and Lys-15, to yield LL37C8, and LL37C12,15, respectively. Carbamylation had profound and diverse effects on the structure and biological properties of LL-37. In some cases, anti-inflammatory LL-37 was rapidly converted to pro-inflammatory LL-37.


Original languageEnglish
JournalInnate immunity
Early online date15 Feb 2016
Publication statusPublished - 22 Mar 2016