Identification and structure-based drug design of cell-active inhibitors of interleukin 17A at a novel C-terminal site.

ABSTRACT: Anti-IL17A therapies have proven effective for numerous inflammatory diseases including psoriasis, axial spondylitis and psoriatic arthritis. Modulating and/or antagonizing protein-protein interactions of IL17A cytokine binding to its cell surface receptors with oral therapies offers the promise to bring forward biologics-like efficacy in a pill to patients. We used an NMR-based fragment screen of recombinant IL17A to uncover starting points for small molecule IL17A antagonist discovery. By examining chemical shift perturbations in 2D [¹H, ¹³C-HSQC] spectra of isotopically labeled IL17A, we discovered fragments binding the cytokine at a previously undescribed site near the IL17A C-terminal region, albeit with weak affinity (> 250 µM). Importantly this binding location

SUBMITTER: Goedken ER 

PROVIDER: S-EPMC9418147 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature