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: 8504510
• 负责人: Sankaran Thayumanavan
• 金额: $ 32.09万
• 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/8504510
• 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; Human; Human Milk; Isoelectric Point; Label; Lead; Ligands; Liquid substance; Malignant Neoplasms; Mass Spectrum Analysis; Methods; Molecular; Organism; Outcome; Peptides; Phase; Physiological; Polymers; Proteins; Protocols documentation; Reporting; Research; Sampling; Serum; Signal Transduction; Solvents; Staging; System; Testing; Therapeutic; Transducers; Translating; Variant; Water; Work; aqueous; base; cancer therapy; design; drug discovery; interest; macromolecule; next generation; novel strategies; public health relevance; receptor; small molecule

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，该提案概述了一种新的超分子方法来解决这一问题。由于在疾病的早期检测方面的意义，检测生理液体中的小浓度生物标记物，如血清，已经引起了人们的极大兴趣。在这个提案中，我们将重点放在基于多肽和蛋白质的生物标记物上，它们的检测对于癌症的早期诊断是有意义的--癌症有效治疗的关键因素。初步结果非常令人鼓舞，我们必须通过了解结合和检测事件背后的因素，为现实生活中的系统进一步发展这一方法。本研究正是围绕这一目的展开的。我们方法的关键要素是：(I)我们的聚合物组件动态地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)这些组件与一组选择性的多肽结合，将它们从水相转移到有机相；(Iii)我们的聚合物提供了信号增强，大大提高了检测的灵敏度；以及(Iv)拟议的实验方案允许同时灵敏地检测几个生物标记物。这些有希望的功能将被严格测试，以检测复杂生理液体、血清和母乳中的癌症生物标记物。请注意，我们专注于成熟的癌症生物标记物，以使我们能够直接专注于测试新方法的多功能性。