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Novel soluble nanopolymers for enrichment of low abundant phosphoproteins

用于富集低丰度磷蛋白的新型可溶性纳米聚合物

基本信息

批准号：
8546309
负责人：
Anton Iliuk
金额：
$ 14.42万
依托单位：
TYMORA ANALYTICAL OPERATIONS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-17 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8546309
关键词：
Address Affinity Binding Biological Assay Biological Markers Cancer Biology Clinical Complex Coupled Dendrimers Detection Development Disease Environment Event Fractionation Goals Human Ions Label Laboratories Location Malignant Neoplasms Mass Spectrum Analysis Metals Methods Modeling Modification Monitor Nature Phase Phospho-Specific Antibodies Phosphopeptides Phosphoproteins Phosphorylation Phosphorylation Site Plasma Polymers Procedures Property Proteins Protocols documentation Quality Control Radioactive Reagent Recovery Reproducibility Research Research Personnel Sampling Sepharose Signal Pathway Signal Transduction Signaling Protein Site Small Business Innovation Research Grant Solid Solutions Source System Techniques Technology Titania Titanium Translational Research United States National Institutes of Health Water anticancer research aqueous base cancer proteomics cancer type chelation combat design functional group improved innovative technologies metal oxide nanoparticle nanopolymer novel phase 1 study phase 2 study product development tool

项目摘要

DESCRIPTION (provided by applicant): With recent technical advances, multiple important signaling pathways that may be the causes of human malignancy have continuously been discovered and dissected. The vast majority of these signaling pathways involve reversible protein phosphorylation, and the information on the location and dynamics of phosphorylation provides important mechanisms on how the signaling networks function and interact. While translational research gradually shifts from lab models to clinical samples, with the ultimate goal of identifying cancer biomarkers, a simple and reliable phosphorylation assay method is still missing for routine detection of phosphorylation in complex and typically heterogeneous clinical samples. Through this NIH SBIR Phase I study we will develop soluble nanopolymer-based reagents, termed PolyMAC (Polymer-based Metal Ion Affinity Capture), into commercial products for the highly efficient isolation of phosphopeptides. This novel design takes advantage of not only the properties of multifunctionalized nanoparticles, but more importantly, the soluble nature of the molecule, allowing for the chelation of a limited amount of phosphopeptides in the solution phase for optimum efficiency and maximum yield. We propose to finalize optimization and scalability of the reagents as commercial products. In addition, high throughput formats for comprehensive phosphoproteomic analyses will be developed to address needs of many cancer biology and proteomics research labs/facilities.

描述(申请人提供)：随着最近的技术进步，可能导致人类恶性肿瘤的多种重要信号通路不断被发现和解剖。这些信号通路中的绝大多数涉及可逆的蛋白质磷酸化，而有关磷酸化位置和动力学的信息为信号网络如何运作和相互作用提供了重要的机制。而转化性研究逐渐从实验室模型转移到临床样本，最终目标是在识别癌症生物标志物方面，目前还缺乏一种简单可靠的磷酸化分析方法来常规检测复杂且典型的异质性临床样本中的磷酸化。通过这项NIH SBIR第一阶段研究，我们将开发基于可溶纳米聚合物的试剂，称为PolyMAC(基于聚合物的金属离子亲和力捕获)，用于高效分离磷酸肽的商业产品。这种新颖的设计不仅利用了多功能纳米颗粒的特性，更重要的是利用了分子的溶解性质，允许在溶液相中螯合有限数量的磷肽，以实现最佳效率和最大产率。我们建议将试剂的优化和可扩展性最终确定为商业化产品。此外，还将开发用于综合磷酸蛋白质组分析的高通量格式，以满足许多癌症生物学和蛋白质组学研究实验室/设施的需求。