PEPTIDE-BASED BORONO LECTINS: NEW TOOLS FOR COLON CANCER

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 该项目的长期目标是开发一种由合成凝集素产生的新型传感器平台，用于结肠癌的检测和诊断。 该方法基于肽骨架上硼酸的差异展示，用于结合癌症相关聚糖和糖蛋白。 硼酸和聚糖之间发生的共价但可逆的相互作用为检测已知在结肠癌肿瘤发生期间发生的异常糖基化事件提供了基础。 这些糖基化模式的识别将通过将多个硼酸部分并入具有不同氨基酸含量的肽骨架中来实现。 选择性和交叉反应性的合成凝集素将通过固相高通量筛选从大肽文库中鉴定，并且可以单独使用或组合使用以提供基于多组分阵列的诊断。 这些新的生物传感器最终将用于检测各种生物环境中存在的碳水化合物的数量和类型，包括血清和组织样本。 具体目标集中在开发1）一种新的合成凝集素库的简易合成策略，2）高通量筛选方法，以及3）传感器阵列的生成和应用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The long term goal of this project is the development of a novel sensor platform, generated from synthetic lectins, for the detection and diagnosis of colon cancer. This approach is based on the differential display of boronic acids on a peptide backbone for binding cancer associated glycans and glycoproteins. The covalent yet reversible interactions that occur between boronic acids and glycans provide the foundation for the detection of abnormal glycosylation events that are known to occur during colon cancer tumorgenesis. The recognition of these glycosylation patterns will be achieved by incorporating multiple boronic acid moieties into a peptide backbone with varying amino acid content. Selective and cross-reactive synthetic lectins will be identified from large peptide libraries, via solid phase high throughput screening, and may be used individually or combined to afford multi-component array-based diagnostics. These new biosensors will ultimately be useful for detecting the number and type of carbohydrates present in a variety of biological contexts, including sera and tissue samples. Specific Aims focus on developing 1) a strategy for the facile synthesis of novel synthetic lectin libraries, 2) methods for high throughput screening, and 3) the generation and application of sensor arrays.