{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T13:27:00Z","timestamp":1791984420791,"version":"4.4.0"},"reference-count":62,"publisher":"American Chemical Society (ACS)","issue":"32","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/V003577\/1"],"award-info":[{"award-number":["BB\/V003577\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/V003577\/2"],"award-info":[{"award-number":["BB\/V003577\/2"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/V006231\/1"],"award-info":[{"award-number":["BB\/V006231\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/V006703\/1"],"award-info":[{"award-number":["BB\/V006703\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/V008412\/1"],"award-info":[{"award-number":["BB\/V008412\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/V008412\/2"],"award-info":[{"award-number":["BB\/V008412\/2"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/Y007816\/1"],"award-info":[{"award-number":["BB\/Y007816\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["A29252"],"award-info":[{"award-number":["A29252"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Novo Nordisk Foundation Center for Protein Design","award":["NNF25SA0105927"],"award-info":[{"award-number":["NNF25SA0105927"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In targeted protein degradation (TPD), specific subcellular proteins are removed by routing them to the ubiquitin-proteasome, autophagy, or lysosome machinery. For instance, proteolysis-targeting chimeras (PROTACs) are synthetic heterobifunctional small molecules that simultaneously bind the target and an E3 ubiquitin ligase to drive ubiquitination and degradation by the proteasome. Despite considerable success, designing such molecules is challenging, and the number of currently addressable ubiquitin E3 ligases is limited. Here, we design a heterobifunctional de novo protein to trigger the degradation of a common cancer target, resulting in a desired phenotypic output. First, we developed a highly stable and adaptable helix\u2013turn\u2013helix scaffold for presenting multiple binding sites. Next, we use computational protein design to incorporate and embellish hot-spot-binding sites to target the antiapoptotic mediators BCL-xL and MCL-1. We show a 75% success rate for creating submicromolar binders against these targets. Crystal structures of the complexes confirmed the designed binding poses. Then, we designed short linear motifs (SLiMs) into the loop of the scaffold to recruit KLHL20 and the ubiquitin ligase machinery. These designs have low micromolar affinity for KLHL20 comparable to that of the natural SLiMs. Moreover, the bifunctionalized proteins degrade BCL-xL in cells, leading to apoptosis.<\/jats:p>","DOI":"10.1021\/jacs.6c07593","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T10:06:45Z","timestamp":1785924405000},"page":"34311-34319","source":"Crossref","is-referenced-by-count":1,"title":["De Novo-Designed Bifunctional\nProteins for Targeted\nProtein Degradation"],"prefix":"10.1021","volume":"148","author":[{"given":"Bram","family":"Mylemans","sequence":"first","affiliation":[{"name":"University of Bristol , , Cantock\u2019s Close , ,","place":["Bristol, U.K., BS8 1TS"]},{"name":"University of Copenhagen , , Jagtvej 160 , ,","place":["Copenhagen, Denmark, 2100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boguslawa","family":"Korona","sequence":"additional","affiliation":[{"name":"University of Cambridge , , ,","place":["Cambridge, U.K., CB2 1PD"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda M.","family":"Acevedo-Jake","sequence":"additional","affiliation":[{"name":"University of Birmingham , , ,","place":["Edgbaston, U.K., B15 2TT"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ailsa","family":"MacRae","sequence":"additional","affiliation":[{"name":"University of Birmingham , , ,","place":["Edgbaston, U.K., B15 2TT"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Edwards","sequence":"additional","affiliation":[{"name":"Larkin University , , 18301 N Miami Ave #1 , , ,","place":["Miami, Florida, U.S.A., 33169"]},{"name":"University of Leeds , , Woodhouse Lane , ,","place":["Leeds, U.K., LS2 9JT"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny T.","family":"Huang","sequence":"additional","affiliation":[{"name":"Cancer Research UK Scotland Institute , Garscube Estate, Switchback Road , ,","place":["Glasgow, U.K., G61 1BD"]},{"name":"University of Glasgow , , Garscube Estate, Switchback Road , ,","place":["Glasgow, U.K., G61 1QH"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9852-6366","authenticated-orcid":true,"given":"Andrew J.","family":"Wilson","sequence":"additional","affiliation":[{"name":"University of Birmingham , , ,","place":["Edgbaston, U.K., B15 2TT"]},{"name":"University of Leeds , , Woodhouse Lane , ,","place":["Leeds, U.K., LS2 9JT"]},{"name":"University of Leeds , , Woodhouse Lane , ,","place":["Leeds, U.K., LS2 9JT"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6504-2576","authenticated-orcid":true,"given":"Laura S.","family":"Itzhaki","sequence":"additional","affiliation":[{"name":"University of Cambridge , , ,","place":["Cambridge, U.K., CB2 1PD"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0394-3202","authenticated-orcid":true,"given":"Derek N.","family":"Woolfson","sequence":"additional","affiliation":[{"name":"University of Bristol , , Cantock\u2019s Close , ,","place":["Bristol, U.K., BS8 1TS"]},{"name":"University of Copenhagen , , Jagtvej 160 , ,","place":["Copenhagen, Denmark, 2100"]},{"name":"University of Bristol , , Medical Sciences Building, University Walk , ,","place":["Bristol, U.K., BS8 1TD"]},{"name":"University of Bristol , , Cantock\u2019s Close , ,","place":["Bristol, U.K., BS8 1TS"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"2026081910243469800_cit1","doi-asserted-by":"publisher","first-page":"5214","DOI":"10.1039\/D2CS00193D","article-title":"PROTACs: past, present and future","volume":"51","author":"Li","year":"2022","journal-title":"Chem. Soc. Rev."},{"key":"2026081910243469800_cit2","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1038\/s41392-022-00966-4","article-title":"Targeted protein\ndegradation: mechanisms, strategies and application","volume":"7","author":"Zhao","year":"2022","journal-title":"Signal Transduction Targeted Ther."},{"key":"2026081910243469800_cit3","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1038\/s41586-020-2545-9","article-title":"Lysosome-targeting chimaeras for degradation\nof extracellular proteins","volume":"584","author":"Banik","year":"2020","journal-title":"Nature"},{"key":"2026081910243469800_cit4","doi-asserted-by":"publisher","first-page":"107926","DOI":"10.1016\/j.jbc.2024.107926","article-title":"How to target membrane\nproteins for degradation: Bringing\nGPCRs into the TPD fold","volume":"300","author":"Korona","year":"2024","journal-title":"J. Biol. Chem."},{"key":"2026081910243469800_cit5","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1038\/s41392-024-02004-x","article-title":"Targeted protein degradation:\nadvances in drug discovery and clinical practice","volume":"9","author":"Zhong","year":"2024","journal-title":"Signal Transduction Targeted Ther."},{"key":"2026081910243469800_cit6","doi-asserted-by":"publisher","first-page":"1064","DOI":"10.1016\/j.chembiol.2024.04.002","article-title":"Molecular glues for protein-protein\ninteractions: Progressing\ntoward a new dream","volume":"31","author":"Konstantinidou","year":"2024","journal-title":"Cell Chem. Biol."},{"key":"2026081910243469800_cit7","doi-asserted-by":"publisher","first-page":"8554","DOI":"10.1073\/pnas.141230798","article-title":"Protacs: Chimeric molecules\nthat target proteins to the Skp1\u2013Cullin\u2013F\nbox complex for ubiquitination and degradation","volume":"98","author":"Sakamoto","year":"2001","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2026081910243469800_cit8","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1038\/s42003-025-08104-w","article-title":"Cellular parameters\nshaping pathways\nof targeted protein degradation","volume":"8","author":"Cardno","year":"2025","journal-title":"Commun. Biol."},{"key":"2026081910243469800_cit9","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1186\/s13045-020-00928-9","article-title":"DT2216\u2500a\nBcl-xL-specific degrader is highly\nactive against Bcl-xL-dependent T cell lymphomas","volume":"13","author":"He","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"2026081910243469800_cit10","doi-asserted-by":"publisher","first-page":"7066","DOI":"10.1039\/D2CS00220E","article-title":"Chemistries of bifunctional\nPROTAC degraders","volume":"51","author":"Cao","year":"2022","journal-title":"Chem. Soc. Rev."},{"key":"2026081910243469800_cit11","doi-asserted-by":"publisher","first-page":"2466","DOI":"10.1016\/j.bmc.2019.02.048","article-title":"Cereblon versus\nVHL: Hijacking E3 ligases against each other using PROTACs","volume":"27","author":"Girardini","year":"2019","journal-title":"Bioorg. Med. Chem."},{"key":"2026081910243469800_cit12","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1038\/s41594-023-01146-w","article-title":"Co-opting the E3 ligase KLHDC2 for targeted\nprotein degradation by\nsmall molecules","volume":"31","author":"Hickey","year":"2024","journal-title":"Nat. Struct. Mol. Biol."},{"key":"2026081910243469800_cit13","doi-asserted-by":"publisher","first-page":"8634","DOI":"10.1021\/acs.jmedchem.5c00295","article-title":"Harnessing the SPOP\nE3 Ubiquitin Ligase via a Bridged Proteolysis\nTargeting Chimera (PROTAC) Strategy for Targeted Protein Degradation","volume":"68","author":"Deng","year":"2025","journal-title":"J. Med. Chem."},{"key":"2026081910243469800_cit14","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.ddtec.2018.12.002","article-title":"SNIPERs\u2500Hijacking\nIAP activity\nto induce protein degradation","volume":"31","author":"Naito","year":"2019","journal-title":"Drug Discovery\nToday: Technol."},{"key":"2026081910243469800_cit15","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1038\/s41573-021-00371-6","article-title":"PROTAC targeted\nprotein degraders:\nthe past is prologue","volume":"21","author":"Be\u0301ke\u0301s","year":"2022","journal-title":"Nat. Rev. Drug Discovery"},{"key":"2026081910243469800_cit16","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1038\/s41419-022-05375-7","article-title":"High-potency PD-1\/PD-L1\ndegradation induced by Peptide-PROTAC in\nhuman cancer cells","volume":"13","author":"Dai","year":"2022","journal-title":"Cell Death Dis."},{"key":"2026081910243469800_cit17","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1101\/gad.349717.122","article-title":"A synthetic KLHL20\nligand to validate CUL3KLHL20 as a potent E3 ligase for targeted protein\ndegradation","volume":"36","author":"Farrell","year":"2022","journal-title":"Genes Dev."},{"key":"2026081910243469800_cit18","doi-asserted-by":"publisher","first-page":"5791","DOI":"10.1073\/pnas.1920251117","article-title":"bioPROTACs as versatile\nmodulators of intracellular therapeutic targets\nincluding proliferating cell nuclear antigen (PCNA)","volume":"117","author":"Lim","year":"2020","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2026081910243469800_cit19","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1016\/j.cell.2023.12.028","article-title":"De novo protein\ndesign; From new structures to programmable functions","volume":"187","author":"Kortemme","year":"2024","journal-title":"Cell"},{"key":"2026081910243469800_cit20","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/j.cbpa.2021.08.004","article-title":"Structure-based protein design with deep learning","volume":"65","author":"Ovchinnikov","year":"2021","journal-title":"Curr. Opin. Chem. Biol."},{"key":"2026081910243469800_cit21","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1038\/s43586-025-00383-1","article-title":"Computational\nprotein design","volume":"5","author":"Albanese","year":"2025","journal-title":"Nat. Rev. Methods Primers"},{"key":"2026081910243469800_cit22","doi-asserted-by":"publisher","first-page":"1631","DOI":"10.1016\/j.str.2025.08.007","article-title":"Code to\ncomplex: AI-driven de novo binder design","volume":"33","author":"Fox","year":"2025","journal-title":"Structure"},{"key":"2026081910243469800_cit23","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein\nstructure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"2026081910243469800_cit24","doi-asserted-by":"publisher","first-page":"100064","DOI":"10.1016\/j.csbr.2025.100064","article-title":"Critical\nassessment of AI-based protein structure prediction: Fundamental challenges\nand future directions in drug discovery","volume":"2","author":"Niazi","year":"2025","journal-title":"Comput.\nStruct. Biotechnol. Rep."},{"key":"2026081910243469800_cit25","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1038\/s41586-023-06415-8","article-title":"De novo design of protein structure and function with RFdiffusion","volume":"620","author":"Watson","year":"2023","journal-title":"Nature"},{"key":"2026081910243469800_cit26","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1126\/science.add2187","article-title":"Robust deep learning\u2013based protein sequence\ndesign using ProteinMPNN","volume":"378","author":"Dauparas","year":"2022","journal-title":"Science"},{"key":"2026081910243469800_cit27","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1038\/s41586-025-09429-6","article-title":"One-shot design of functional\nprotein binders with BindCraft","volume":"646","author":"Pacesa","year":"2025","journal-title":"Nature"},{"key":"2026081910243469800_cit28","doi-asserted-by":"publisher","first-page":"2625","DOI":"10.1038\/s41467-023-38328-5","article-title":"Improving de novo protein\nbinder design with deep learning","volume":"14","author":"Bennett","year":"2023","journal-title":"Nat. Commun."},{"key":"2026081910243469800_cit29","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1038\/s41586-022-04654-9","article-title":"Design of protein-binding\nproteins from the target structure alone","volume":"605","author":"Cao","year":"2022","journal-title":"Nature"},{"key":"2026081910243469800_cit30","doi-asserted-by":"publisher","first-page":"3019","DOI":"10.1016\/j.csbj.2022.06.021","article-title":"Computational\ndesign of an apoptogenic\nprotein that binds BCL-xL and MCL-1 simultaneously and potently","volume":"20","author":"Kim","year":"2022","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"2026081910243469800_cit31","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1038\/s41589-025-02083-z","article-title":"Accurate single-domain\nscaffolding of three nonoverlapping protein\nepitopes using deep learning","volume":"22","author":"Castro","year":"2026","journal-title":"Nat. Chem. Biol."},{"key":"2026081910243469800_cit32","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1038\/s41586-024-07948-2","article-title":"Designed endocytosis-inducing\nproteins degrade targets and amplify\nsignals","volume":"638","author":"Huang","year":"2025","journal-title":"Nature"},{"key":"2026081910243469800_cit33","doi-asserted-by":"publisher","DOI":"10.1101\/2025.10.13.681693","article-title":"Multiplex design and discovery of\nproximity handles\nfor programmable proteome editing","author":"Suiter","year":"2025","journal-title":"bioRxiv"},{"key":"2026081910243469800_cit34","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.1038\/s41587-025-02761-2","article-title":"Target sequence-conditioned\ndesign of peptide binders using masked\nlanguage modeling","volume":"44","author":"Chen","year":"2026","journal-title":"Nat. Biotechnol."},{"key":"2026081910243469800_cit35","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1038\/s41392-025-02176-0","article-title":"The BCL2 family: from\napoptosis mechanisms to new advances in targeted\ntherapy","volume":"10","author":"Vogler","year":"2025","journal-title":"Signal Transduction Targeted Ther."},{"key":"2026081910243469800_cit36","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1038\/s41580-023-00629-4","article-title":"Mechanisms\nof BCL-2 family proteins in mitochondrial\napoptosis","volume":"24","author":"Czabotar","year":"2023","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2026081910243469800_cit37","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1007\/s10495-014-1051-7","article-title":"The Bcl-2 family:\nstructures, interactions and targets\nfor drug discovery","volume":"20","author":"Kvansakul","year":"2015","journal-title":"Apoptosis"},{"key":"2026081910243469800_cit38","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1812939115","article-title":"Peptide design by optimization\non a data-parameterized protein interaction\nlandscape","volume":"115","author":"Jenson","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026081910243469800_cit39","doi-asserted-by":"publisher","first-page":"1644","DOI":"10.1016\/j.cell.2014.04.034","article-title":"A Computationally Designed\nInhibitor of an Epstein-Barr Viral Bcl-2\nProtein Induces Apoptosis in Infected Cells","volume":"157","author":"Procko","year":"2014","journal-title":"Cell"},{"key":"2026081910243469800_cit40","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abe1682","article-title":"Cell-penetrating Alphabody protein scaffolds for intracellular drug\ntargeting","volume":"7","author":"Pannecoucke","year":"2021","journal-title":"Sci. Adv."},{"key":"2026081910243469800_cit41","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abm7375","article-title":"Efficacy and specificity\nof inhibitors of BCL-2 family protein interactions\nassessed by affinity measurements in live cells","volume":"8","author":"Osterlund","year":"2022","journal-title":"Sci. Adv."},{"issue":"45","key":"2026081910243469800_cit42","doi-asserted-by":"publisher","DOI":"10.1002\/chem.202400430","article-title":"Design, Synthesis, and\nEvaluation of BCL-2 Targeting PROTACs","volume":"30","author":"Bricelj","year":"2024","journal-title":"Chem.\n- Eur. J."},{"key":"2026081910243469800_cit43","doi-asserted-by":"publisher","first-page":"1938","DOI":"10.1038\/s41591-019-0668-z","article-title":"A selective BCL-XL PROTAC degrader achieves safe and potent antitumor\nactivity","volume":"25","author":"Khan","year":"2019","journal-title":"Nat. Med."},{"key":"2026081910243469800_cit44","doi-asserted-by":"publisher","DOI":"10.64898\/2025.12.22.695764","article-title":"Coiled-coil\nscaffolds for Targeted Protein Degradation","author":"Korona","year":"2026","journal-title":"bioRxiv"},{"issue":"9","key":"2026081910243469800_cit45","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1016\/j.str.2019.06.005","article-title":"Structural Basis for Recruitment of DAPK1 to the KLHL20\nE3 Ligase","volume":"27","author":"Chen","year":"2019","journal-title":"Structure"},{"key":"2026081910243469800_cit46","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1038\/s41589-024-01642-0","article-title":"Rationally seeded computational\nprotein design of a-helical barrels","volume":"20","author":"Albanese","year":"2024","journal-title":"Nat. Chem.\nBiol."},{"key":"2026081910243469800_cit47","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1038\/s41589-022-01076-6","article-title":"De novo designed peptides for cellular delivery and subcellular localisation","volume":"18","author":"Rhys","year":"2022","journal-title":"Nat. Chem. Biol."},{"key":"2026081910243469800_cit48","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1002\/pro.2610","article-title":"Rapid search for tertiary fragments\nreveals protein\nsequence\u2013structure relationships","volume":"24","author":"Zhou","year":"2015","journal-title":"Protein\nSci."},{"key":"2026081910243469800_cit49","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024109","article-title":"RosettaRemodel: A Generalized\nFramework for Flexible Backbone Protein\nDesign","volume":"6","author":"Huang","year":"2011","journal-title":"PLoS One"},{"key":"2026081910243469800_cit50","doi-asserted-by":"publisher","first-page":"7656","DOI":"10.1039\/C8SC02643B","article-title":"De novo coiled-coil peptides as scaffolds for\ndisrupting protein\u2013protein\ninteractions","volume":"9","author":"Fletcher","year":"2018","journal-title":"Chem. Sci"},{"key":"2026081910243469800_cit51","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1021\/acschembio.5c00137","article-title":"Grafted Coiled-Coil\nPeptides as Multivalent Scaffolds for Protein\nRecognition","volume":"20","author":"Acevedo-Jake","year":"2025","journal-title":"ACS Chem. Biol."},{"key":"2026081910243469800_cit52","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1006\/jmbi.1993.1648","article-title":"Shape Complementarity\nat Protein\/Protein Interfaces","volume":"234","author":"Lawrence","year":"1993","journal-title":"J. Mol. Biol."},{"key":"2026081910243469800_cit53","doi-asserted-by":"publisher","first-page":"3031","DOI":"10.1021\/acs.jctc.7b00125","article-title":"The Rosetta All-Atom\nEnergy Function for Macromolecular Modeling\nand Design","volume":"13","author":"Alford","year":"2017","journal-title":"J. Chem. Theory Comput."},{"key":"2026081910243469800_cit54","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1186\/s13045-020-01007-9","article-title":"MCL-1 inhibitors, fast-lane\ndevelopment of a new class of anti-cancer\nagents","volume":"13","author":"Bolomsky","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"2026081910243469800_cit55","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/0022-1759(95)00072-I","article-title":"A novel assay\nfor apoptosis Flow cytometric detection of phosphatidylserine expression\non early apoptotic cells using fluorescein labelled Annexin V","volume":"184","author":"Vermes","year":"1995","journal-title":"J. Immunol. Methods"},{"key":"2026081910243469800_cit56","doi-asserted-by":"publisher","first-page":"6598","DOI":"10.1038\/s41467-025-62050-z","article-title":"De novo designed protein guiding targeted protein degradation","volume":"16","author":"Li","year":"2025","journal-title":"Nat. Commun."},{"key":"2026081910243469800_cit57","doi-asserted-by":"publisher","first-page":"10336","DOI":"10.1021\/acs.jmedchem.4c00828","article-title":"A Top-Down Design Approach\nfor Generating a Peptide PROTAC Drug Targeting\nAndrogen Receptor for Androgenetic Alopecia Therapy","volume":"67","author":"Ma","year":"2024","journal-title":"J. Med. Chem."},{"key":"2026081910243469800_cit58","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202507092","article-title":"Reengineering\nof a Proteomimetic Pan-Ras Inhibitor into a Ras Degrader","volume":"64","author":"Ongkingco","year":"2025","journal-title":"Angew. Chem. Int. Ed."},{"key":"2026081910243469800_cit59","doi-asserted-by":"publisher","first-page":"6819","DOI":"10.1021\/acs.chemrev.5c00046","article-title":"From Concepts\nto Inhibitors: A Blueprint for Targeting Protein\u2013Protein Interactions","volume":"125","author":"Hong","year":"2025","journal-title":"Chem. Rev."},{"key":"2026081910243469800_cit60","doi-asserted-by":"publisher","DOI":"10.1101\/2025.04.17.648362","article-title":"Crowdsourced Protein Design:\nLessons\nFrom the Adaptyv EGFR Binder Competition","author":"Cotet","year":"2025","journal-title":"bioRxiv"},{"key":"2026081910243469800_cit61","doi-asserted-by":"publisher","first-page":"2198","DOI":"10.1021\/acschembio.4c00418","article-title":"AlphaFold Ensemble\nCompetition Screens Enable Peptide Binder Design with Single-Residue\nSensitivity","volume":"19","author":"Vosbein","year":"2024","journal-title":"ACS Chem. Biol."},{"key":"2026081910243469800_cit62","doi-asserted-by":"publisher","first-page":"2008.2014.670059","DOI":"10.1101\/2025.08.14.670059","article-title":"Predicting\nExperimental Success in De Novo Binder Design: A Meta-Analysis of\n3,766 Experimentally Characterised Binders","author":"Overath","year":"2025","journal-title":"bioRxiv"}],"container-title":["Journal of the American\nChemical Society"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/jacs.6c07593","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jacsat\/article-pdf\/148\/32\/34311\/66403930\/jacs.6c07593.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jacsat\/article-pdf\/148\/32\/34311\/66403930\/jacs.6c07593.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T14:48:43Z","timestamp":1787150923000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jacsat\/article\/148\/32\/34311\/5245217\/De-Novo-Designed-Bifunctional-Proteins-for"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,5]]},"references-count":62,"journal-issue":{"issue":"32","published-online":{"date-parts":[[2026,8,5]]},"published-print":{"date-parts":[[2026,8,19]]}},"URL":"https:\/\/doi.org\/10.1021\/jacs.6c07593","relation":{},"ISSN":["0002-7863","1520-5126"],"issn-type":[{"value":"0002-7863","type":"print"},{"value":"1520-5126","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,5]]}}}