PEPTIDE-BASED BORONO LECTINS: NEW TOOLS FOR COLON CANCER

基于肽的硼凝集素：治疗结肠癌的新工具

• 批准号: 8167870
• 负责人: PAUL M THOMPSON
• 金额: $ 16.35万
• 依托单位: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167870
• 关键词: Affinity; Binding; Biocompatible; Biological Assay; Biosensor; Boronic Acids; Cancer Diagnostics; Carbohydrates; Cell surface; Colon Carcinoma; Complex; Computer Retrieval of Information on Scientific Projects Database; Detection; Development; Diagnostic; Diagnostic tests; Disease; Funding; Grant; Institution; Lead; Lectin; Malignant Neoplasms; Methods; Nature; Optics; Peptide Library; Peptides; Polysaccharides; Process; Protein Chemistry; Randomized; Reagent; Research; Research Personnel; Resources; Series; Serum; Solid; Source; Techniques; Therapeutic; Tissues; United States National Institutes of Health; Vertebral column; base; combinatorial; design; novel; novel diagnostics; response; sensor; small molecule; sugar; tool

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Proposed in this project is the development of a novel biosensor for the detection of colon cancer. Specifically, the design, synthesis and analysis of a series of Peptide-based Borono Lectins are described. These reagents will be able to detect cancer associated glycans in sera and ultimately on tissues. This project is being pursued because a number of glycans are abnormally expressed in colon cancer and the current methods for carbohydrate detection are cumbersome. The approach described herein, which combines proven and promising methods from the fields of protein chemistry, small molecule sensor design, and advanced optical processing techniques, will generate a novel and biocompatible diagnostic agent. This method takes advantage of Nature's own building blocks and binding scenarios (namely peptides and sugar-lectin interactions respectively), for the creation of a new diagnostic to detect glycans abnormally expressed in colon cancer. Use of a peptide backbone enables a highly modular approach capable of readily changing the geometry, valency and binding affinity of the lectin which allows for rapid access to several different binding scenarios within the sensor and therefore the ability to swiftly assay for new and different targets. Randomized peptide libraries incorporating phenyl boronic acids will be synthesized and used to screen for binding with a number of simple and complex cancer associated glycans. This is a high throughput combinatorial approach that is expected to lead to the identification of sugar-specific and cross-reactive lectins. These borono-lectins are conjugated to a solid support and as such will be used to generate a novel biosensor platform for the detection of abnormal levels of specific saccharides present in sera. Successful development of this proposal has the potential to revolutionize colon cancer diagnostics. In a number of disease states, including colon cancer, the levels and types of serum and cell surface glycans (i.e. sugars) are abnormal. This proposal takes a high throughput, combinatorial approach to generate and screen Peptide-based Borono-Lectins (PBLs) for specific saccharide recognition. Successful completion of this project will provide an efficient diagnostic test to simply and rapidly identify the presence and/or extent of colon cancer; thereby aiding the development of an appropriate therapeutic response. .

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 该项目提出开发一种用于检测结肠癌的新型生物传感器。 具体来说，描述了一系列基于肽的硼诺凝集素的设计、合成和分析。 这些试剂将能够检测血清中并最终检测组织中与癌症相关的聚糖。该项目正在进行中，因为许多聚糖在结肠癌中异常表达，并且目前的碳水化合物检测方法很麻烦。 本文描述的方法结合了蛋白质化学、小分子传感器设计和先进光学处理技术领域经过验证和有前景的方法，将产生一种新颖的生物相容性诊断剂。 该方法利用了 Nature 自身的构建模块和结合场景（分别是肽和糖-凝集素相互作用），创建了一种新的诊断方法来检测结肠癌中异常表达的聚糖。 使用肽主链可以实现高度模块化的方法，能够轻松改变凝集素的几何形状、化合价和结合亲和力，从而可以快速访问传感器内的几种不同的结合场景，从而能够快速检测新的和不同的靶标。 将合成包含苯基硼酸的随机肽库，并用于筛选与许多简单和复杂的癌症相关聚糖的结合。 这是一种高通量组合方法，有望实现糖特异性和交叉反应凝集素的鉴定。 这些硼凝集素与固体支持物缀合，因此将用于生成新型生物传感器平台，用于检测血清中存在的特定糖的异常水平。 该提案的成功开发有可能彻底改变结肠癌的诊断。 在包括结肠癌在内的许多疾病状态下，血清和细胞表面聚糖（即糖）的水平和类型是异常的。 该提案采用高通量组合方法来生成和筛选基于肽的硼酸凝集素 (PBL)，以进行特定糖识别。 该项目的成功完成将提供有效的诊断测试，以简单快速地识别结肠癌的存在和/或程度；从而帮助形成适当的治疗反应。 。