PEPTIDE-BASED BORONO LECTINS: NEW TOOLS FOR COLON CANCER

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 本项目旨在开发一种用于结肠癌检测的新型生物传感器。具体地说，描述了一系列基于多肽的硼凝集素的设计、合成和分析。这些试剂将能够检测血清中的癌症相关多糖，并最终在组织上检测到。这个项目之所以被推进，是因为结肠癌中有许多糖链异常表达，而目前的碳水化合物检测方法很繁琐。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的光学处理技术领域经过验证和前景看好的方法，将产生一种新型的生物相容性诊断试剂。这种方法利用了大自然自己的积木和结合场景(即分别是肽和糖-凝集素的相互作用)，创建了一种新的诊断方法，以检测结肠癌中异常表达的糖链。使用多肽骨架能够实现高度模块化的方法，能够容易地改变凝集素的几何结构、价态和结合亲和力，从而允许快速访问传感器内的几个不同的结合场景，从而能够快速检测新的和不同的靶标。含有苯基硼酸的随机肽库将被合成，并用于筛选与许多简单和复杂的癌症相关糖链的结合。这是一种高通量的组合方法，有望导致糖特异性和交叉反应凝集素的鉴定。这些硼-凝集素被连接到固体载体上，因此将被用来产生一种新的生物传感器平台，用于检测血清中存在的异常水平的特定糖类。这项提议的成功开发有可能给结肠癌诊断带来革命性的变化。 在许多疾病状态中，包括结肠癌，血清和细胞表面糖链(即糖)的水平和类型都是异常的。该方案采用高通量的组合方法来产生和筛选用于特定糖识别的基于多肽的硼-凝集素(PBL)。该项目的成功完成将提供一种有效的诊断测试，以简单和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. .