Identifying Synthetic Lectins from a Competitive Screen for the Detection of Prostate Cancer

Abstract

Herein, we report a dual dye competitive screening method for the identification of five boronic acid functionalized synthetic lectins (SLs) that are selective for prostate-associated targets with the goal of detecting and staging prostate cancer. This method uses differently labeled normal (RWEP-1) and diseased (PC3) cell membrane extracts in a competitive binding assay to identify SLs that bind either the cancerous or normal extracts but not both. Subsequent studies examined the efficacy of these new SL hits in an array format to discriminate six prostate cell lines. The SL array was able to (a) classify the prostate cell lines with 83% accuracy, (b) discriminate the same cell lines based on their metastatic potential (noncancerous/healthy, cancerous/lowly metastatic, and cancerous/metastatic) with 96% classification accuracy, and (c) exhibit enhanced selectivity for prostate-derived versus colon-derived cell lines. Further analysis delineated the contribution from each SL in these studies, providing a focused SL array having potential utility as a cancer diagnostic.

Advances in glycopeptide enrichment methods for the analysis of protein glycosylation over the past decade

“…Boronic acids have been used to purify ribonucleotides and other cis-diol-containing molecules [98,99]. The ligand of m-aminophenyl-boronic acid binds to the cis-diol group of the sugar moiety of nucleotides or glycoproteins, forming a reversible pentagon ring complex [100,101]. Commonly used boronic acid compounds are 3-aminophenylboronic acid (APBA) and 4-vinylphenylboronic acid (VPBA) [98].…”