Geraths Christian, Christen Erik H, Weber Wilfried
Faculty of Biology and BIOSS Center for Biological Signalling Studies, University of Freiburg, Schänzlestrasse 18, 79104 Freiburg, Germany.
Macromol Rapid Commun. 2012 Dec 21;33(24):2103-8. doi: 10.1002/marc.201200563. Epub 2012 Oct 19.
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.
能够检测病理代谢物浓度并通过释放治疗性刺激做出反应的代谢物响应水凝胶在治疗代谢性疾病方面具有很大的前景。在本研究中,描述了一种水凝胶,它能够区分痛风性关节炎的病原体尿酸在生理浓度和病理浓度之间的差异。该水凝胶是通过将源自耐辐射球菌的尿酸阻遏物HucR的二聚体变体与线性聚丙烯酰胺偶联而合成的。蛋白质接枝聚合物通过特异性结合HucR的多聚体hucO DNA序列[hucO]n交联形成水凝胶。在尿酸浓度升高时,HucR从[hucO]n上解离,从而削弱水凝胶结构并导致其溶解。