Abstract
Interleukin-17A (IL-17A) is a principal driver of multiple inflammatory and immune disorders. Antibodies that neutralize IL-17A or its receptor (IL-17RA) deliver efficacy in autoimmune diseases, but no small-molecule IL-17A antagonists have yet progressed into clinical trials. Investigation of a series of linear peptide ligands to IL-17A and characterization of their binding site has enabled the design of novel macrocyclic ligands that are themselves potent IL-17A antagonists.
MeSH terms
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Algorithms
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Binding Sites
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Cells, Cultured
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Drug Design
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Humans
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Interleukin-17 / antagonists & inhibitors*
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Interleukin-17 / chemistry*
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Keratinocytes / cytology
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Keratinocytes / drug effects
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Keratinocytes / metabolism
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Macrocyclic Compounds / chemistry
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Macrocyclic Compounds / pharmacology
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Molecular Dynamics Simulation
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Peptides, Cyclic / chemistry
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Peptides, Cyclic / pharmacology*
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Protein Binding
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Small Molecule Libraries / chemistry
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Small Molecule Libraries / pharmacology*
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Structure-Activity Relationship
Substances
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IL17A protein, human
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Interleukin-17
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Macrocyclic Compounds
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Peptides, Cyclic
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Small Molecule Libraries