@article{31d2625271544044a531efbfb8d56e15,
title = "Computationally designed high specificity inhibitors delineate the roles of BCL2 family proteins in cancer",
abstract = "Many cancers overexpress one or more of the six human pro-survival BCL2 family proteins to evade apoptosis. To determine which BCL2 protein or proteins block apoptosis in different cancers, we computationally designed three-helix bundle protein inhibitors specific for each BCL2 pro-survival protein. Following in vitro optimization, each inhibitor binds its target with high picomolar to low nanomolar affinity and at least 300-fold specificity. Expression of the designed inhibitors in human cancer cell lines revealed unique dependencies on BCL2 proteins for survival which could not be inferred from other BCL2 profiling methods. Our results show that designed inhibitors can be generated for each member of a closely-knit protein family to probe the importance of specific protein-protein interactions in complex biological processes.",
author = "Stephanie Berger and Erik Procko and Daciana Margineantu and Lee, {Erinna F.} and Shen, {Betty W.} and Alex Zelter and Silva, {Daniel Adriano} and Kusum Chawla and Herold, {Marco J.} and Garnier, {Jean Marc} and Richard Johnson and Maccoss, {Michael J.} and Guillaume Lessene and Davis, {Trisha N.} and Stayton, {Patrick S.} and Stoddard, {Barry L.} and Fairlie, {W. Douglas} and Hockenbery, {David M.} and David Baker",
note = "Funding Information: National Institutes of Health P41GM103533 Stephanie Berger Erik Procko David Baker Defense Threat Reduction Agency HDTRA1-10-0040 Stephanie Berger Erik Procko David Baker Howard Hughes Medical Institute HHMI-027779 Stephanie Berger Erik Procko David Baker National Science Foundation Graduate Research Fellowship Program Stephanie Berger Worldwide Cancer Research 15-0025 Erinna F Lee W Douglas FairlieCancer Council Victoria 1057949 Erinna F Lee W Douglas Fairlie Pew Charitable Trusts Daniel-Adriano Silva Consejo Nacional de Ciencia y Tecnologia Daniel-Adriano Silva National Health and Medical Research Council 1024620 Erinna F Lee Australian Research Council FT150100212 Erinna F Lee National Institutes of Health R01 GM115545 Betty W Shen Barry L Stoddard National Institutes of Health R01 CA158921-04 Daciana Margineantu David M Hockenbery Victorian Government, Australia Operational Infrastructure Support Program Erinna F Lee W Douglas Fairlie Publisher Copyright: {\textcopyright} Berger et al.",
year = "2016",
month = nov,
day = "2",
doi = "10.7554/eLife.20352",
language = "English (US)",
volume = "5",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
number = "NOVEMBER2016",
}