Targeting phosphatidylserine on apoptotic cells with phages and peptides selected from a bacteriophage display library

Mol Imaging. Nov-Dec 2007;6(6):417-26.

Abstract

Phosphatidylserine (PS) is a well-characterized biomarker for apoptosis. Ligands that bind to PS can be used for noninvasive imaging of therapy-induced cell death, particularly apoptosis. In this study, we screened a random 12-mer peptide phage library on liposomes prepared from PS. One clone displaying the peptide SVSVGMKPSPRP (designated as PS3-10) bound to PS approximately 4-fold better than its binding to phosphatidylcholine and 18-fold better than to bovine serum albumin in a solid-phase binding assay. In addition, the binding of the corresponding PS3-10 peptide to PS was significantly higher than that of a scrambled peptide. PS3-10 phages, but not a control 4-2-2 phage, bound to aged red blood cells that had PS exposed on their surface. Binding of PS3-10 phages and PS3-10 peptide to TRAIL-induced apoptotic DLD1 cells was 3.2 and 5.4 times higher than their binding to untreated viable cells, respectively. Significantly, immunohistochemical staining confirmed selective binding of PS3-10 phages to apoptotic cells. Our data suggest that panning of phage display libraries may allow the selection of suitable peptide ligands for apoptotic cells and that PS3-10 peptide may serve as a template for further development of molecular probes for in vitro and in vivo imaging of apoptosis.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Apoptosis / physiology*
  • Bacteriophage M13 / metabolism*
  • Cellular Senescence / physiology
  • Diagnostic Imaging / methods*
  • Drug Delivery Systems*
  • Erythrocytes / drug effects
  • Erythrocytes / physiology
  • Humans
  • Membrane Glycoproteins / metabolism
  • Peptide Library*
  • Peptides / analysis
  • Peptides / metabolism*
  • Phosphatidylserines / metabolism*
  • Protein Binding
  • Sequence Homology, Amino Acid
  • TNF-Related Apoptosis-Inducing Ligand / pharmacology
  • Tumor Cells, Cultured

Substances

  • Membrane Glycoproteins
  • Peptide Library
  • Peptides
  • Phosphatidylserines
  • TNF-Related Apoptosis-Inducing Ligand