Targeting protein-protein interactions: Lessons from p53/MDM2. Export

@article{citeulike:1644037, abstract = {The tremendous challenge of inhibiting therapeutically important protein-protein interactions has created the opportunity to extend traditional medicinal chemistry to a new class of targets and to explore nontraditional strategies. Here we review a widely studied system, the interaction between tumor suppressor p53 and its natural antagonist MDM2, for which both traditional and nontraditional approaches have been reported. This system has been a testing ground for novel proteomimetic scaffold-based strategies, i.e., for attempts to mimic the recognition surface displayed by a folded protein with unnatural oligomers. Retroinverso peptides, peptoids, terphenyls, beta-hairpins, p-oligobenzamides, beta-peptides, and miniproteins have all been explored as inhibitors of the p53/MDM2 interaction, and we focus on these oligomer-based efforts. Traditional approaches have been successful as well, and we briefly review small molecule inhibitors along with other strategies for reactivation of the p53 pathway, for comparison with oligomer- based approaches. We close with comments on an emerging dichotomy among protein-protein interaction targets. (c) 2007 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 88: 657-686, 2007.This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com.}, address = {Department of Chemistry, University of Wisconsin, 1101 University Avenue, Madison, WI 53706.}, author = {Murray, Justin K K. and Gellman, Samuel H H.}, citeulike-article-id = {1644037}, citeulike-linkout-0 = {http://dx.doi.org/10.1002/bip.20741}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/17427181}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=17427181}, citeulike-linkout-3 = {http://www3.interscience.wiley.com/cgi-bin/abstract/114208783/ABSTRACT}, day = {10}, doi = {10.1002/bip.20741}, issn = {0006-3525}, journal = {Biopolymers}, keywords = {interaction, mdm2, molecule, p53, protein, small}, month = {April}, number = {5}, pages = {657--686}, posted-at = {2007-09-11 12:32:46}, priority = {2}, title = {Targeting protein-protein interactions: Lessons from p53/MDM2.}, url = {http://dx.doi.org/10.1002/bip.20741}, volume = {88}, year = {2007} }

TY - JOUR ID - citeulike:1644037 L3 - citeulike-article-id:1644037 N2 - The tremendous challenge of inhibiting therapeutically important protein-protein interactions has created the opportunity to extend traditional medicinal chemistry to a new class of targets and to explore nontraditional strategies. Here we review a widely studied system, the interaction between tumor suppressor p53 and its natural antagonist MDM2, for which both traditional and nontraditional approaches have been reported. This system has been a testing ground for novel proteomimetic scaffold-based strategies, i.e., for attempts to mimic the recognition surface displayed by a folded protein with unnatural oligomers. Retroinverso peptides, peptoids, terphenyls, beta-hairpins, p-oligobenzamides, beta-peptides, and miniproteins have all been explored as inhibitors of the p53/MDM2 interaction, and we focus on these oligomer-based efforts. Traditional approaches have been successful as well, and we briefly review small molecule inhibitors along with other strategies for reactivation of the p53 pathway, for comparison with oligomer- based approaches. We close with comments on an emerging dichotomy among protein-protein interaction targets. (c) 2007 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 88: 657-686, 2007.This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com. IS - 5 JF - Biopolymers SN - 0006-3525 AD - Department of Chemistry, University of Wisconsin, 1101 University Avenue, Madison, WI 53706. EP - 686 TI - Targeting protein-protein interactions: Lessons from p53/MDM2. VL - 88 SP - 657 KW - interaction KW - mdm2 KW - molecule KW - p53 KW - protein KW - small AU - Murray, Justin K AU - Gellman, Samuel H PY - 2007/04/10/ UR - http://dx.doi.org/10.1002/bip.20741 ER -