Screening of a library of phage-displayed peptides identifies human bcl-2 as a taxol-binding protein

J Mol Biol. 1999 Jan 8;285(1):197-203. doi: 10.1006/jmbi.1998.2303.


A random library of phage displayed peptides was screened for binding to a biotinylated derivative of paclitaxel (Taxol). Affinity-selected peptides were analyzed for similarity to human proteins. There was no significant similarity between the paclitaxel-selected peptides and tubulin. However, a subset of the peptides was identified that exhibits significant similarity to a non-conserved region of the anti-apoptotic human protein Bcl-2: ELISA assays confirmed binding of paclitaxel to Bcl-2, and circular dichroism spectroscopy demonstrated that a substantial conformational change accompanies this binding. In vivo, treatment with paclitaxel has been shown to lead to Bcl-2 inactivation with concomitant phosphorylation of residues in a disordered, regulatory loop region of the protein. Similarity between paclitaxel-selected peptides and this loop region implicate these residues in drug binding, and suggest that the apoptotic action of paclitaxel may involve the binding of paclitaxel to Bcl-2. These results demonstrate that peptides displayed on the surface of bacteriophage particles can mimic the ligand-binding properties of disordered regions of proteins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Antineoplastic Agents, Phytogenic / metabolism*
  • Bacteriophages
  • Circular Dichroism
  • Consensus Sequence
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Molecular Sequence Data
  • Paclitaxel / metabolism*
  • Peptide Library
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*


  • Antineoplastic Agents, Phytogenic
  • Peptide Library
  • Proto-Oncogene Proteins c-bcl-2
  • Paclitaxel