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

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.