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.
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