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

@article{citeulike:2797343, abstract = {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.}, address = {Institute of Molecular Biophysics, Florida State University, Tallahassee, FL, 32306, USA.}, author = {Rodi, D. J. and Janes, R. W. and Sanganee, H. J. and Holton, R. A. and Wallace, B. A. and Makowski, L. }, citeulike-article-id = {2797343}, doi = {10.1006/jmbi.1998.2303}, issn = {0022-2836}, journal = {Journal of molecular biology}, keywords = {taxol, usa}, month = {January}, number = {1}, pages = {197--203}, posted-at = {2008-05-14 11:14:23}, priority = {2}, title = {Screening of a library of phage-displayed peptides identifies human bcl-2 as a taxol-binding protein.}, url = {http://dx.doi.org/10.1006/jmbi.1998.2303}, volume = {285}, year = {1999} }

TY - JOUR ID - citeulike:2797343 L3 - citeulike-article-id:2797343 TI - Screening of a library of phage-displayed peptides identifies human bcl-2 as a taxol-binding protein. JF - Journal of molecular biology VL - 285 IS - 1 SP - 197 EP - 203 AD - Institute of Molecular Biophysics, Florida State University, Tallahassee, FL, 32306, USA. SN - 0022-2836 N2 - 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. KW - taxol KW - usa AU - Rodi, DJ AU - Janes, RW AU - Sanganee, HJ AU - Holton, RA AU - Wallace, BA AU - Makowski, L PY - 1999/01/08/ UR - http://dx.doi.org/10.1006/jmbi.1998.2303 ER -