Toward a Diagnostic Immunoassay Specific for Prostate Cancer: Chemical Synthesis of Homogeneous N-Linked Prostate Specific Antigen Glycopeptides

摘要

Current prostate cancer (PCa) diagnostic tools are unsatisfactory because of their inability to determine the root cause of elevated levels of prostate specific antigen (PSA), which can arise from benign or malignant conditions. The purpose of the research described is the development of an improved PCa immunoassay based on errant PSA glycoform expression in prostatic cancer cells. Specifically, the aim is to define and implement a strategy for the synthesis of normal and transformed PSA glycopeptides, and to employ the PSA glycopeptides in immunological studies targeting the generation of antibodies that differentiate between normal and cancerous PSA. Such differentiating antibodies would comprise the sought-after improved PCa diagnostic. The first round of synthetic studies is complete: a strategy has been defined for the chemical synthesis of complex glycans and glycopeptides, including PSA-based glycopeptides. The synthetic strategy has been applied successfully to the syntheses of normal and transformed fragments of PSA. A collaboration is currently underway, during which the PSA glycopeptides will be conjugated with a carrier protein (keyhole limpet hemocyanin, KLH), and attempts will be made to generate antibodies that can differentiate between normal and transformed glycoforms of PSA.