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）：识别特定分子并报告它们在复杂混合物中的存在是一项重大挑战，该提案概述了解决该问题的新超分子方法。由于对疾病早期检测的影响，人们对检测生理液体（例如血清）中小浓度的生物标志物产生了极大的兴趣。在这项提案中，我们重点关注基于肽和蛋白质的生物标志物，其检测对于癌症的早期诊断很有意义，而癌症的早期诊断是有效癌症治疗的关键因素。初步结果非常令人鼓舞，我们有必要通过了解结合和检测事件背后的因素来进一步开发这种适用于现实系统的方法。拟议的研究就是围绕这一目的进行的。我们方法的关键要素是：（i）我们的聚合物组件在动力学上被捕获在组装的溶剂中，并在广泛的条件下保持其超分子保真度； (ii) 这些组装体与一组选择性的肽结合，将它们从水相转移到有机相； (iii) 我们的聚合物提供信号增强功能，大大提高检测的灵敏度； (iv)所提出的实验方案允许灵敏地同时检测多种生物标志物。这些有前途的功能将接受严格的测试，以检测复杂的生理液体、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，以便我们能够专注于测试新方法的多功能性。