Disulfide-constrained peptides that bind to the extracellular portion of the prostate-specific membrane antigen

Shawn E. Lupold, Ronald Rodriguez

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

The prostate-specific membrane antigen (PSMA) is a well-characterized surface antigen, overexpressed in the most advanced, androgen-resistant human prostate cancer cells. We sought to exploit PSMA cell surface properties as a target for short peptides that will potentially guide protein-based therapeutics, such as viral vectors, to prostate cancer cells. Two separate phage display peptide strategies were applied, in parallel, to purified PSMA protein bound to two separate substrates. We reasoned that peptide sequences common to both substrate selections would be specific binders of PSMA. Additionally, the design allowed for stringent cross-selections, where phage populations from one selection condition could be applied to the alternative substrate. These strategies resulted in a series of phage displayed peptides able to bind to PSMA by ELISA and direct binding assays, both with purified protein and in prostate cancer cells. Cell binding is competitively inhibited by purified PSMA. The synthesized peptides are capable of enhancing PSMA carboxypeptidase enzymatic activity, suggesting protein folding stabilization. The discovery of these peptides provides the foundation for subsequent development of peptide targeted therapeutics against prostate cancer.

Original languageEnglish (US)
Pages (from-to)597-603
Number of pages7
JournalMolecular cancer therapeutics
Volume3
Issue number5
Publication statusPublished - May 1 2004

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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