Separation of enzymatically active and inactive prostate-specific antigen (PSA) by peptide affinity chromatography

Prostate. 2004 Mar 1;58(4):345-53. doi: 10.1002/pros.10337.

Abstract

Background: Prostate-specific antigen (PSA) is a serine protease with highly prostate-specific expression and an important marker for prostate cancer. We have previously identified novel PSA-binding peptides that enhance the enzymatic activity of PSA when produced as fusion proteins.

Method: PSA-binding peptides and derivatives with a spacer were chemically synthesized and used to prepare an affinity column, which was used to fractionate PSA in seminal plasma, serum, and LNCap cell culture medium.

Results: Approximately 67% of seminal plasma PSA bound to the peptide affinity column and was eluted under mild conditions. Eluted PSA was intact and enzymatically active while the unbound fraction mainly contained various nicked forms. ProPSA from LNCap cells bound to the peptide column only after activation by trypsin.

Conclusions: PSA-binding peptides can be used to separate enzymatically active and inactive forms of PSA. Thus the peptides are potentially useful as ligands for development of methods for specific detection of active free PSA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / isolation & purification
  • Chromatography, Affinity / methods
  • Chromatography, Ion Exchange
  • Humans
  • Isoenzymes / chemistry
  • Isoenzymes / isolation & purification
  • Isoenzymes / metabolism
  • Kinetics
  • Male
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / chemistry
  • Prostate-Specific Antigen / blood
  • Prostate-Specific Antigen / chemistry
  • Prostate-Specific Antigen / isolation & purification*
  • Prostate-Specific Antigen / metabolism*
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / diagnosis
  • Semen / chemistry

Substances

  • Biomarkers, Tumor
  • Isoenzymes
  • Peptide Fragments
  • Prostate-Specific Antigen