Similarity between the sequences of taxol-selected peptides and the disordered loop of the anti-apoptotic protein, Bcl-2.
The anti-cancer drug taxol is known to bind to and induce the polymerization of tubulin and has recently been shown to bind to the anti-apoptotic protein Bcl-2, but not to its homolog, Bcl-XL. Libraries of random peptides displayed on the surface of a bacteriophage were screened to select those exhibiting affinity for taxol. The sequences of these peptides were compared to sequences of proteins involved in mitosis and apoptosis. No significant similarities were detected between the sequences of tubulins and the taxol-selected peptides. However, a high level of similarity exists between the selected peptides and the disordered loop of Bcl-2. Conversely, there was little similarity between the sequences of the selected peptides and Bcl-XL. These results indicate that peptides displayed on the surface of a bacteriophage can mimic the ligand-binding behavior of a disordered protein loop and that comparison of the sequences of affinity-selected peptides with protein sequences can be predictive for ligand binding.
Rodi
D J
DJ
Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida 32306, USA.
Makowski
L
L
D000595:Amino Acid Sequence; D017209:Apoptosis; D001435:Bacteriophages; D001665:Binding Sites; D006801:Humans; D008969:Molecular Sequence Data; D017239:Paclitaxel / Q000737:chemistry* / Q000493:pharmacokinetics*; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry* / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012984:Software; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D019151:Peptide Library; D010455:Peptides; D019253:Proto-Oncogene Proteins c-bcl-2; D014764:Viral Proteins; D051020:bcl-X Protein; D017239:Paclitaxel