Protein-Catalyzed Capture Agents for Improved Malaria Diagnostics

用于改进疟疾诊断的蛋白质催化捕获剂

• 批准号: 9236069
• 负责人: David Nelson Bunck
• 金额: $ 5.71万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9236069
• 关键词: Address; Adsorption; Affinity; Amino Acids; Antibodies; Antigens; Architecture; Area; Binding; Binding Proteins; Biological Assay; Biological Markers; Blood; Blood Circulation; Blood Tests; Blood specimen; Calorimetry; Cells; Chemicals; Complex; Country; Detection; Development; Devices; Diagnosis; Diagnostic; Disease; Environment; Epitopes; Eye; HRP-2 protein; Human; Immobilization; Isotopes; Kinetics; Lactate Dehydrogenase; Lateral; Lead; Ligands; Malaria; Measures; Membrane; Modification; Molecular; Molecular Structure; NMR Spectroscopy; Oligopeptides; Paper; Patients; Performance; Plasmodium; Plasmodium falciparum; Point Mutation; Population; Process; Proteins; Reagent; Reporter; Research; Resources; Sensitivity and Specificity; Solid; Spectrum Analysis; Structure; Surface Plasmon Resonance; System; Testing; Thermodynamics; Titrations; Training; Validation; Wit; Work; assay development; base; design; disease diagnosis; experimental study; improved; insight; iterative design; malaria infection; nanoparticle; public health relevance; stoichiometry; success

 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.

 描述（由申请人提供）：我们将开发新的蛋白质催化捕获（PCC）试剂，用于检测人血液中恶性疟原虫疟疾株的两种重要生物标志物。PCC试剂是一类新兴的寡肽，其可以区分活细胞内仅具有单个氨基酸点突变的靶标。这 一项提案将利用它们的选择性来开发富含组氨酸的蛋白2和乳酸盐的结合剂 脱氢酶。我们将针对每种蛋白质上的多个表位开发PCC试剂，以说明疟疾流行国家内固有的区域多样性，并验证其在人类血液中的选择性。这些筛选的候选铅将进行完整的分子表征，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像。最后，这些线索将被纳入侧流分析，着眼于在低资源地区的实施。我们的设备的成功将根据其可靠检测人体血液中生物标志物的能力进行评估，并将作为基于这些材料开发其他疾病靶点检测方法的概念验证。