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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（由申请人提供）：随着最近的技术进步，可能是人类恶性肿瘤原因的多种重要信号通路已被不断发现和剖析。这些信号通路中的绝大多数涉及可逆的蛋白质磷酸化，并且关于磷酸化的位置和动力学的信息提供了关于信号网络如何起作用和相互作用的重要机制。而转化研究逐渐从实验室模型转向临床样本，最终目标是在鉴定癌症生物标志物方面，仍然缺少简单可靠的磷酸化测定方法，用于复杂和典型异质性临床样品中磷酸化的常规检测。通过这项NIH SBIR第一阶段研究，我们将开发可溶性纳米聚合物基试剂，称为PolyMAC（聚合物基金属离子亲和捕获），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化纳米颗粒的特性，更重要的是利用了分子的可溶性，允许在溶液相中螯合有限量的磷酸肽，以获得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产品。此外，将开发用于全面磷酸化蛋白质组学分析的高通量格式，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。