{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T12:32:17Z","timestamp":1787142737297,"version":"build-2736575974"},"reference-count":58,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry A European J"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>This work addresses the question if supramolecular systems can be tailored to interfere with posttranslational modifications (PTM) and epigenetics. As a prominent example, the efficient epigenetic control operative in nucleosome\u2010DNA interactions was selected. Conceptually, transcription activation by specific acetylation of strategic lysine residues on the Histone H4 protein is replaced by noncovalent inclusion of the respective lysine residues inside the cavities of designed molecular tweezers. To this end, novel dimeric molecular tweezers with functional linkers were designed, which exhibit nanomolar affinity to the DNA\u2010binding fragment of histone H4. Fluorescence titrations and ITC measurements provide experimental evidence for high selectivity over other lysine\u2010containing H4 areas. Notably, rigid short linkers with hydrogen bond donors outperform flexible peptidic connections. MD simulations identified new binding motifs involving attractive interactions between H4 residues and linker functionalities. The ability of modified tweezers to interrupt the essential histone\u2010DNA interaction was demonstrated in a fluorescence anisotropy assay. In addition, the most powerful tweezers with high H4 affinity were subjected to a competitive enzymatic HAT experiment, where they successfully competed for lysine binding sites and impaired HAT function. Thus, powerful new histone binders were developed which act as supramolecular PTM on a histone H4 peptide.<\/jats:p>","DOI":"10.1002\/chem.71588","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T12:02:46Z","timestamp":1787140966000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modulation of Epigenetic Control by Advanced Molecular Tweezers"],"prefix":"10.1002","author":[{"family":"My\u2010Hue\u2010Le","sequence":"first","affiliation":[{"name":"Institute of Organic Chemistry I Faculty of Chemistry University of Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9594-1492","authenticated-orcid":false,"given":"Bianca","family":"Kamba","sequence":"additional","affiliation":[{"name":"Structural and Medicinal Biochemistry Faculty of Biology University of Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Matena","sequence":"additional","affiliation":[{"name":"Structural and Medicinal Biochemistry Faculty of Biology University of Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7513-7384","authenticated-orcid":false,"given":"Christine","family":"Beuck","sequence":"additional","affiliation":[{"name":"Structural and Medicinal Biochemistry Faculty of Biology University of Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0146-2577","authenticated-orcid":false,"given":"Victoria","family":"Momand","sequence":"additional","affiliation":[{"name":"Structural and Medicinal Biochemistry Faculty of Biology University of Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spiros","family":"Salvanos","sequence":"additional","affiliation":[{"name":"Structural and Medicinal Biochemistry Faculty of Biology University of Duisburg\u2010Essen  Essen Germany"},{"name":"Functional Biochemistry Faculty of Biology Institute of Molecular Biology II University of Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Vossen","sequence":"additional","affiliation":[{"name":"Structural and Medicinal Biochemistry Faculty of Biology University of Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8963-256X","authenticated-orcid":false,"given":"Mike","family":"Blueggel","sequence":"additional","affiliation":[{"name":"Structural and Medicinal Biochemistry Faculty of Biology University of Duisburg\u2010Essen  Essen Germany"},{"name":"Functional Biochemistry Faculty of Biology Institute of Molecular Biology II University of Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7003-6362","authenticated-orcid":false,"given":"Thomas","family":"Schrader","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry I Faculty of Chemistry University of Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0435-7202","authenticated-orcid":false,"given":"Peter","family":"Bayer","sequence":"additional","affiliation":[{"name":"Structural and Medicinal Biochemistry Faculty of Biology University of Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr500392w"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.7b01979"},{"key":"e_1_2_12_4_1","doi-asserted-by":"crossref","first-page":"3577","DOI":"10.1039\/b710425a","article-title":"Design and Synthesis of \u03b1\u2010helical Peptides and Mimetics","volume":"5","author":"Garner J.","year":"2007","journal-title":"Organic & Biomolecular Chemistry"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9OB01801H"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1039\/c1cc11541c"},{"issue":"5","key":"e_1_2_12_7_1","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1002\/ange.200904413","article-title":"Protein Dimerization Induced by Supramolecular Interactions with Cucurbit [8] Uril","volume":"122","author":"Nguyen H. 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