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

Abstract

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.

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Document Details

Document Type
Technical Report
Publication Date
Mar 01, 2004
Accession Number
ADA425738

Entities

People

  • Justin S. Miller

Organizations

  • Memorial Sloan Kettering Cancer Center

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Biomedical Research
  • Carbohydrates
  • Chemical Synthesis
  • Chemistry
  • Glycoconjugates
  • Liquid Chromatography
  • Mass Spectrometry
  • Neoplasms
  • Organic Chemistry
  • Prostate
  • Prostate Cancer
  • Proteins

Fields of Study

  • Chemistry

Readers

  • Immunology
  • Molecular and Cellular Biochemistry
  • Prostate Cancer Biology.