Zsila, Ferenc and Kohut, Gergely and Beke-Somfai, Tamás (2019) Disorder-to-helix conformational conversion of the human immunomodulatory peptide LL-37 induced by antiinflammatory drugs, food dyes and some metabolites. INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, 129. pp. 50-60. ISSN 0141-8130
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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. The 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, where LL-37 is partially folded, these small molecules 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 of LL-37 in the accommodation of ligand 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 of related cationic peptides.
Item Type: | Article |
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Uncontrolled Keywords: | Circular Dichroism; ANTIINFLAMMATORY DRUGS; Hemin; bile acid; LL-37; INTRINSIC DISORDER; Food dyes; Helical folding; |
Subjects: | Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3015 Molecular biology / molekuláris biológia |
SWORD Depositor: | MTMT SWORD |
Depositing User: | MTMT SWORD |
Date Deposited: | 13 Feb 2019 12:37 |
Last Modified: | 30 May 2019 23:15 |
URI: | http://real.mtak.hu/id/eprint/91265 |
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