Supramolecular Assemblies for Detecting Biomarkers in Complex Mixtures

用于检测复杂混合物中生物标志物的超分子组件

• 批准号: 9039005
• 负责人: Sankaran Thayumanavan
• 金额: $ 31.95万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9039005
• 关键词: Address; Area; Binding; Biological; Biological Markers; Buffers; Cancer Detection; Cancer Patient; Chemistry; Complement; Complex; Complex Mixtures; Detection; Disease; Early Diagnosis; Elements; Environment; Event; Goals; Health; Human; Human Milk; Isoelectric Point; Label; Lead; Ligands; Liquid substance; Malignant Neoplasms; Mass Spectrum Analysis; Methods; Molecular; Organism; Outcome; Peptides; Phase; Physiological; Polymers; Protein Engineering; Proteins; Protocols documentation; Reporting; Research; Sampling; Serum; Signal Transduction; Solvents; Staging; System; Testing; Therapeutic; Transducers; Translating; Variant; Water; Work; aqueous; base; cancer biomarkers; cancer therapy; design; drug discovery; interest; macromolecule; next generation; novel strategies; receptor; small molecule; specific biomarkers

DESCRIPTION (provided by applicant): Recognizing specific molecules and reporting their presence in a complex mixture is a significant challenge, and this proposal outlines a new supramolecular approach to address this problem. There has been a great interest in detecting biomarkers in small concentrations in physiological fluids, such as serum, because of the implications in early detection of diseases. In this proposal, we focus on peptide- and protein-based biomarkers, the detection of which is of interest in the early diagnosis of cancer - a criticl factor in effective cancer treatment. The preliminary results are very encouraging and it is essential that we further develop this approach for real-life systems by understanding the factors that underlie the binding and detection events. The proposed research is focused on this purpose. The key elements of our approach are that: (i) our polymer assemblies are kinetically trapped in the assembled solvent and maintain their supramolecular fidelity under a broad range of conditions; (ii) these assemblies bind to a selective set of peptides to move them from the aqueous to the organic phase; (iii) our polymers provide signal enhancements that greatly enhance the sensitivity of detection; and (iv) the proposed experimental protocols allow for concurrent detection of several biomarkers sensitively. These promising features will be rigorously tested for detecting cancer biomarkers in complex physiological fluids, serum and breast milk. Note that we focus on well-established cancer biomarkers to allow us to focus squarely on testing the versatility of new approach.

描述（由申请人提供）：识别特定的分子并报告它们在复杂混合物中的存在是一个重大挑战，该提案概述了一种新的超分子方法来解决此问题。由于对疾病的早期发现具有影响，因此人们对在生理流体（例如血清）中以较少浓度的生物标志物（例如血清）的浓度非常感兴趣。在此提案中，我们专注于基于肽和蛋白质的生物标志物，其检测是对癌症的早期诊断感兴趣的 - 这是有效癌症治疗的批评因素。初步结果非常令人鼓舞，我们必须通过了解构成约束和检测事件的因素来进一步为现实生活系统开发这种方法。拟议的研究重点是此目的。我们方法的关键要素是：（i）我们的聚合物组件在组装的溶剂中被捕获，并在广泛的条件下保持其超分子忠诚度； （ii）这些组件与选择性的一组肽结合，将它们从水性移到有机相； （iii）我们的聚合物提供了信号增强功能，可大大增强检测的敏感性； （iv）提出的实验方案允许同时检测几种生物标志物。这些有希望的特征将经过严格测试，以检测复杂的生理液，血清和母乳中的癌症生物标志物。请注意，我们专注于成熟的癌症生物标志物，使我们能够将重点放在测试新方法的多功能上。