Disorder-to-helix conformational conversion of the human immunomodulatory peptide LL-37 induced by antiinflammatory drugs, food dyes and some metabolites

Ferenc Zsila, Gergely Kohut, Tamás Beke-Somfai

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The human antimicrobial and immunomodulatory peptide LL-37 is ubiquitously expressed and secreted by epithelial cells of mucosal surfaces including the gastrointestinal tract, the primary absorption site of orally administered drugs and food components. Besides antimicrobial properties, LL-37 also contributes to the pathophysiology of various diseases such as ulcerative colitis, Crohn's disease and cancer. Non-covalent association of antiinflammatory drugs, porphyrin pigments, bile salts and food dyes to the peptide was uncovered and evaluated by circular dichroism (CD) spectroscopy. These agents induce the disorder-to-order conformational transition of the natively unstructured LL-37 leading to its helical folding. Even in the presence of chloride ions, when LL-37 is partially folded, the inducers were able to rise the α-helix content. CD titration data indicated positive cooperativity between the ligand molecules accommodated to the peptide chain resulting in multimeric complexes with apparent dissociation constants ranged from 2 to 500 μM. Computational docking suggested the prominent role of the Lys8-Arg19 segment in the accommodation of small molecules, governed principally by salt bridges and H-bonding. Since pleiotropic biological functions of LL-37 are strongly conformation-dependent, it could be anticipated that folding inducer compounds may modulate its in vivo actions and also of related cationic peptides.

Original languageEnglish
Pages (from-to)50-60
Number of pages11
JournalInternational Journal of Biological Macromolecules
Volume129
DOIs
Publication statusPublished - May 15 2019

Keywords

  • Antiinflammatory drugs
  • Bile acid
  • Circular dichroism
  • Food dyes
  • Helical folding
  • Hemin
  • Intrinsic disorder
  • LL-37

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Economics and Econometrics
  • Energy(all)

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