Endothelium-derived C-type natriuretic peptide possesses cytoprotective and anti-atherogenic functions that regulate vascular homeostasis. The vasoprotective effects of C-type natriuretic peptide are somewhat mediated by the natriuretic peptide receptor C, suggesting that this receptor represents a novel therapeutic target for the treatment of cardiovascular diseases. In order to facilitate our drug discovery efforts, we have optimized an array of biophysical methods including surface plasmon resonance, fluorescence polarization and thermal shift assays to aid in the design, assessment and characterization of small molecule agonist interactions with natriuretic peptide receptors. Assay conditions are investigated to explore the feasibility and dynamic range of each method, and peptide-based agonists and antagonists are used as controls to validate these conditions. Once established, each technique was compared and contrasted with respect to their drug discovery utility. We foresee that such techniques will facilitate the discovery and development of potential therapeutic agents for NPR-C and other large extracellular domain membrane receptors.

中文翻译：

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细胞外结构域肽受体的生物物理筛选方法，应用于利钠肽受体C配体。

内皮来源的C型利钠肽具有调节血管稳态的细胞保护和抗动脉粥样硬化功能。C型利钠肽的血管保护作用在某种程度上由利钠肽受体C介导，表明该受体代表了治疗心血管疾病的新型治疗靶标。为了促进我们的药物发现工作，我们优化了一系列生物物理方法，包括表面等离振子共振，荧光偏振和热位移分析，以帮助设计，评估和表征与利钠肽受体的小分子激动剂相互作用。研究测定条件以探索每种方法的可行性和动态范围，使用基于肽的激动剂和拮抗剂作为对照来验证这些条件。一旦建立起来，就对每种技术的药物发现效用进行比较和对比。我们预见，此类技术将促进NPR-C和其他大型胞外域膜受体的潜在治疗剂的发现和开发。