Synthetic Lectins: New Tools for Detection and Management of Prostate Cancer
Annual rept. 19 Jul 2013-18 Jul 2014
SOUTH CAROLINA RESEARCH FOUNDATION COLUMBIA
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Among US men, prostate cancer is the most common cancer besides non-malignant skin cancer, afflicting over 200,000 each year, and is the second leading cause of cancer-related death, over 30,000 per year. Thus, our long term goal is to develop synthetic lectin SL arrays for the detection and diagnosis of prostate cancer. We are pursuing this goal because healthy and diseased cells produce different biomarkers, which provide unique signatures by which these cells can be distinguished. Taking advantage of the fact that aberrant protein glycosylation is a hallmark of cancer we propose to develop a novel sensor platform that can be used to detect Cancer Associated GlycansGlycoproteins for the diagnosis of prostate cancer. The basis of this diagnostic is the differential display of boronic acids on peptides and peptoids. Boronic acids are used because they form covalent yet reversible bonds with specific structural motifs i.e., diols present on all Cancer Associated GlycansGlycoproteins. The covalent interaction increases the affinity of the SL for the target Cancer Associated GlycansGlycoproteins, while the peptidepeptoid backbone and preorganization of the boronic acids define the selectivity of binding. Building on preliminary data, which demonstrated the ability to identify synthetic lectins, assemble them into an array, and discriminate between normal, cancerous and metastatic colon cancer cell lines, we will 1 generate synthetic lectins that recognize specific Cancer Associated GlycansGlycoproteins 2 probe the biochemical and biophysical basis for the glycan-SL interactions to enhance binding affinities and selectivities and 3 create multi-component sensor arrays to differentiate cell and tissue types to diagnose and monitor prostate cancer.
- Medicine and Medical Research