A hydrogel sensing pathological urate concentrations

Metabolite-responsive hydrogels that detect pathological metabolite concentrations and react by releasing a therapeutic stimulus hold high promises in treating metabolic diseases. In this study, a hydrogel is described that discriminates between physiological and pathological concentrations of urate, the causative agent of gouty arthritis. The hydrogel is synthesized by coupling a dimeric variant of the Deinococcus radiodurans-derived urate repressor HucR to linear polyacrylamide. The protein-grafted polymer is crosslinked to form a hydrogel by a multimeric hucO DNA sequence [hucO]n specifically binding HucR. At elevated urate concentrations, HucR dissociates from [hucO]n thereby weakening the hydrogel structure and resulting in its dissolution. A stimulus-responsive biohybrid material is described that rapidly dissolves at pathological concentrations of the gouty arthritis-causing metabolite urate. The gel consists of polyacrylamide and DNA that are crosslinked by the Deinococcus radiodurans-derived urate sensor HucR, which binds its specific target DNA motif at physiological urate concentrations and dissociates thereof at pathological concentrations. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.