PEPTIDE-BASED BORONO LECTINS: NEW TOOLS FOR COLON CANCER

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本计画提出发展一种新的大肠癌侦测生物感测器。 具体而言，设计，合成和分析的一系列肽为基础的硼凝集素的描述。 这些试剂将能够检测血清中并最终检测组织中的癌症相关聚糖。该项目正在进行中，因为许多聚糖在结肠癌中异常表达，并且目前检测碳水化合物的方法很麻烦。 本文所述的方法结合了来自蛋白质化学、小分子传感器设计和先进的光学处理技术领域的经证实和有前途的方法，将产生新型和生物相容的诊断剂。 这种方法利用了自然界自己的构建块和结合方案（即肽和糖-凝集素相互作用），用于创建新的诊断方法来检测结肠癌中异常表达的聚糖。 肽骨架的使用实现了能够容易地改变凝集素的几何形状、化合价和结合亲和力的高度模块化方法，这允许快速接近传感器内的几种不同的结合情况，因此能够快速测定新的和不同的靶标。 将合成并入苯基硼酸的随机化肽文库，并用于筛选与许多简单和复杂的癌症相关聚糖的结合。 这是一种高通量的组合方法，预计将导致糖特异性和交叉反应性凝集素的鉴定。 这些borono-lectin缀合到固体支持物上，因此将用于产生用于检测血清中存在的特异性抗体的异常水平的新型生物传感器平台。 该提案的成功开发有可能彻底改变结肠癌诊断。 在许多疾病状态中，包括结肠癌，血清和细胞表面聚糖（即糖）的水平和类型是异常的。 该提议采用高通量的组合方法来产生和筛选用于特异性糖识别的基于肽的硼凝集素（PBL）。 该项目的成功完成将提供一种有效的诊断测试，以简单快速地确定结肠癌的存在和/或程度;从而帮助制定适当的治疗反应。 .

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. .