Synthetic Lectins: New Tools for Detection and Management of Prostate Cancer

Abstract

Abstract : 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 Glycans/Glycoproteins 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 Glycans/Glycoproteins. The covalent interaction increases the affinity of the SL for the target Cancer Associated Glycans/Glycoproteins, while the peptide/peptoid 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 Glycans/Glycoproteins; (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. The development of these synthetic lectins is highly significant because they can be used to generate an array based diagnostic that has the potential to revolutionize the early diagnosis of prostate cancer