Protein-Catalyzed Capture Agents for Improved Malaria Diagnostics

 描述(申请人提供)：我们将开发新的蛋白质催化捕获(PCC)试剂，用于检测人类血液中恶性疟原虫品系的两个重要生物标记物。PCC试剂是一类新兴的寡肽，可以区分活细胞内只有一个氨基酸点突变的靶标。这 提案将利用他们的选择性开发富含组氨酸的蛋白2和乳酸的结合剂 脱氢酶。我们将为每个蛋白质上的多个表位开发PCC试剂，以解释疟疾流行国家内在的区域多样性，并验证它们在人类血液中的选择性。来自这些筛选的候选铅将受到完整的分子表征，以获得其选择性和灵敏度背后的热力学和动力学的准确图景。最后，这些铅将被纳入侧向流动分析，着眼于在低资源地区实施。我们的设备的成功将根据它们可靠地检测人类血液中的生物标记物的能力进行评估，并将作为基于这些材料开发其他疾病目标分析的概念证明。

 DESCRIPTION (provided by applicant): We will develop new protein-catalyzed capture (PCC) agents for the detection of two important biomarkers of the Plasmodium falciparium strain of malaria in human blood. PCC agents are an emerging class of oligopeptides that can discriminate between targets with only a single amino acid point mutation within living cells. This proposal will leverage their selectivity to develop binders to histidine-rich protein 2 and lactate dehydrogenase. We will develop PCC agents for multiple epitopes on each protein to account for inherent regional diversity within malaria endemic countries and validate their selectivity in human blood. Lead candidates from these screens will be subjected to full molecular characterization to gain an accurate picture of the thermodynamics and kinetics behind their selectivity and sensitivity. Finally, these leads will be incorporated into lateral flow assays wit an eye towards implementation in low-resource areas. The success of our devices will be evaluated on their ability to reliably detect biomarkers in human blood and will serve as a proof of concept for the development of assays for other disease targets based on these materials.