{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T15:03:42Z","timestamp":1789139022739,"version":"build-2803163510"},"reference-count":37,"publisher":"American Chemical Society (ACS)","issue":"29","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000266","name":"UK Research and Innovation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000332","name":"Royal Society of Edinburgh","doi-asserted-by":"publisher","award":["R221397"],"award-info":[{"award-number":["R221397"]}],"id":[{"id":"10.13039\/501100000332","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008134","name":"Office of the Royal Society","doi-asserted-by":"publisher","award":["RGS\/R1\/231182"],"award-info":[{"award-number":["RGS\/R1\/231182"]}],"id":[{"id":"10.13039\/501100008134","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000704","name":"Royal Society of Chemistry","doi-asserted-by":"publisher","award":["D24-7367946572"],"award-info":[{"award-number":["D24-7367946572"]}],"id":[{"id":"10.13039\/501100000704","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008078","name":"University of Strathclyde","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008078","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100023964","name":"Johnson Matthey","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100023964","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Homeobox protein Hox-B13 (HOXB13) is an oncogenic transcription factor that is associated with prostate cancer risk. Unlike most transcription factors (TFs), HOXB13 is a methyl-plus TF and has been shown to be preferentially recruited to DNA prostate cancer risk loci. Here, we miniaturized HOXB13 to create metal-stapled mimetics that can target its cognate primary DNA-binding site in a sequence-specific, methyl-sensitive manner. Targeted profiling of 5-methylcytosine (5mC) recognition using V269X mimetic mutants revealed that leucine can further enhance both methyl sensitivity and methyl specificity through methyl\u2013methyl contact with 5mC and decreased methyl\u2013pi interactions with cytosine. Collectively, our study revealed novel insights into the molecular interactions of HOXB13 with methylated DNA and new tools that will provide a structural basis for future development of a new class of sequence-specific methylated DNA binders.<\/jats:p>","DOI":"10.1021\/jacs.6c01290","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T10:45:46Z","timestamp":1784025946000},"page":"30785-30792","source":"Crossref","is-referenced-by-count":1,"title":["Miniaturized HOXB13\nMimetics Are Sequence-Specific,\nMethyl-Sensitive DNA Binders"],"prefix":"10.1021","volume":"148","author":[{"given":"Claire","family":"Wong","sequence":"first","affiliation":[{"name":"University of Strathclyde , , ,","place":["Glasgow, U.K., G1 1XL"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3600-0497","authenticated-orcid":true,"given":"Shiao Y.","family":"Chow","sequence":"additional","affiliation":[{"name":"University of Strathclyde , , ,","place":["Glasgow, U.K., G1 1XL"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"2026073021323726400_cit1","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.gde.2017.02.007","article-title":"Transcription Factor\u2013DNA Binding:\nBeyond Binding Site Motifs","volume":"43","author":"Inukai","year":"2017","journal-title":"Current Opinion\nGenetics Development"},{"issue":"5","key":"2026073021323726400_cit2","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/s0092-8674(00)81532-9","article-title":"Methylation-Induced\nRepression--Belts, Braces, and Chromatin","volume":"99","author":"Bird","journal-title":"Cell"},{"issue":"2","key":"2026073021323726400_cit3","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1007\/s00018-002-8420-z","article-title":"DNA Methylation\nand the Regulation\nof Gene Transcription","volume":"59","author":"Attwood","year":"2002","journal-title":"Cellular Molecular Life\nSciences"},{"issue":"1","key":"2026073021323726400_cit4","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1101\/gad.947102","article-title":"DNA Methylation\nPatterns and Epigenetic Memory","volume":"16","author":"Bird","year":"2002","journal-title":"Genes &\ndevelopment"},{"issue":"9","key":"2026073021323726400_cit5","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1038\/nrg.2016.83","article-title":"Transcription Factors as Readers\nand Effectors of DNA Methylation","volume":"17","author":"Zhu","year":"2016","journal-title":"Nat. Rev.\nGenet"},{"issue":"6","key":"2026073021323726400_cit6","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1042\/EBC20190033","article-title":"Sensitivity of Transcription Factors to DNA Methylation","volume":"63","author":"He\u0301berle\u0301","year":"2019","journal-title":"Essays Biochem."},{"issue":"6337","key":"2026073021323726400_cit7","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaj2239","article-title":"Impact of Cytosine Methylation on\nDNA Binding Specificities of Human Transcription Factors","volume":"356","author":"Yin","year":"2017","journal-title":"Science"},{"issue":"18","key":"2026073021323726400_cit8","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaf949","article-title":"Systematic Identification\nof Regions Where DNA Methylation\nIs Correlated with Transcription Refines Regulatory Logic in Normal\nand Tumour Tissues","volume":"53","author":"Heery","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"2026073021323726400_cit9","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.sbi.2018.06.004","article-title":"Detecting and Interpreting DNA Methylation Marks","volume":"53","author":"Ren","year":"2018","journal-title":"Curr. Opin. Struct. Biol."},{"key":"2026073021323726400_cit10","doi-asserted-by":"publisher","DOI":"10.1177\/1176935119828776","article-title":"Correlation\nPatterns\nBetween DNA Methylation and Gene Expression in The Cancer Genome Atlas","volume":"18","author":"Spainhour","year":"2019","journal-title":"Cancer Inform."},{"issue":"4","key":"2026073021323726400_cit11","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1073\/pnas.0509843102","article-title":"Defining the Sequence-Recognition\nProfile of DNA-Binding Molecules","volume":"103","author":"Warren","year":"2006","journal-title":"Proc. Natl.\nAcad. Sci. U. S. 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Chem."},{"issue":"6","key":"2026073021323726400_cit33","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1093\/nar\/gkg249","article-title":"The Affinity of Different MBD\nProteins for a Specific Methylated Locus Depends on Their Intrinsic\nBinding Properties","volume":"31","author":"Fraga","year":"2003","journal-title":"Nucleic Acids Res."},{"issue":"1","key":"2026073021323726400_cit34","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-23585-z","article-title":"Interaction Preferences\nbetween Protein Side Chains\nand Key Epigenetic Modifications 5-Methylcytosine, 5-Hydroxymethycytosine\nand N6-Methyladenine","volume":"12","author":"Hajnic","year":"2022","journal-title":"Sci. Rep."},{"issue":"3","key":"2026073021323726400_cit35","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1021\/cr040669e","article-title":"Proteases\nUniversally Recognize Beta\nStrands In Their Active Sites","volume":"105","author":"Tyndall","year":"2005","journal-title":"Chem. 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Biol."}],"container-title":["Journal of the American\nChemical Society"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/jacs.6c01290","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jacsat\/article-pdf\/148\/29\/30785\/66344729\/jacs.6c01290.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jacsat\/article-pdf\/148\/29\/30785\/66344729\/jacs.6c01290.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T08:11:09Z","timestamp":1785485469000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jacsat\/article\/148\/29\/30785\/5237519\/Miniaturized-HOXB13-Mimetics-Are-Sequence-Specific"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,14]]},"references-count":37,"journal-issue":{"issue":"29","published-online":{"date-parts":[[2026,7,14]]},"published-print":{"date-parts":[[2026,7,29]]}},"URL":"https:\/\/doi.org\/10.1021\/jacs.6c01290","relation":{"has-preprint":[{"id-type":"doi","id":"10.26434\/chemrxiv.15000479\/v1","asserted-by":"object"}]},"ISSN":["0002-7863","1520-5126"],"issn-type":[{"value":"0002-7863","type":"print"},{"value":"1520-5126","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,14]]}}}