AI Article Synopsis
- The IL-17 cytokine family is important in various immune and autoimmune diseases, making it a key focus for diagnostics and therapies.
- Researchers developed specific ligands that can differentiate between human IL-17F and IL-17A by identifying unique epitopes on each protein.
- The study successfully created macrocyclic peptide binders with high selectivity and affinity for IL-17F and IL-17A, offering a method for targeting complex epitopes like those recognized by B cell receptors.
Article Abstract
The IL-17 cytokine family is associated with multiple immune and autoimmune diseases and comprises important diagnostic and therapeutic targets. This work reports the development of epitope-targeted ligands designed for differential detection of human IL-17F and its closest homologue IL-17A. Non-overlapping and unique epitopes on IL-17F and IL-17A were identified by comparative sequence analysis of the two proteins. Synthetic variants of these epitopes were utilized as targets for in situ click screens against a comprehensive library of synthetic peptide macrocycles with 5-mer variable regions. Single generation screens yielded selective binders for IL-17F and IL-17A with low cross-reactivity. Macrocyclic peptide binders against two distinct IL-17F epitopes were coupled using variable length chemical linkers to explore the physical chemistry of cooperative binding. The optimized linker length yielded a picomolar affinity binder, while retaining high selectivity. The presented method provides a rational approach towards targeting discontinuous epitopes, similar to what is naturally achieved by many B cell receptors.
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| http://dx.doi.org/10.1002/chem.201704752 | DOI Listing |
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