{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T13:05:12Z","timestamp":1789736712066,"version":"4.0.1"},"reference-count":62,"publisher":"Wiley","issue":"35","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry A European J"],"published-print":{"date-parts":[[2026,9,19]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Protein\u2010protein interactions that regulate gene expression in the nucleus are increasingly recognized as potential therapeutic targets but present unique challenges. Effective targeting requires molecules capable of interacting with large protein surfaces while remaining small enough to pass through the nuclear pore, for which peptidomimetics are promising candidates.\n                    <jats:italic>De novo<\/jats:italic>\n                    design strategies often focus on projecting hot\u2010spot residues using well\u2010defined, rigid scaffolds; however, other critical properties\u2014such as solubility, charge, or local flexibility\u2014are often overlooked. Our approach employs \u03b1\/\u03b2\u2010peptidomimetics to enable fine\u2010tuning of these properties by generating manageable\u2010sized soluble libraries. Using the KIX domain of the coactivator proteins p300\/CBP as a model system, we demonstrate that our strategy allows modular optimization of hot\u2010spot, solvent\u2010exposed, and structure\u2010inducing residues, thereby tuning affinity and binding\u2010site selectivity. Coactivator proteins often use multivalency to enhance affinity and selectivity, which we exploit by creating dimers from our initial hits. We show that both static libraries and template\u2010directed dynamic covalent chemistry facilitate the screening of multivalent ligands that closely mimic the native interaction partners. Our design strategy, built on \u03b1\/\u03b2\u2010peptide building blocks, represents a promising approach to develop de novo ligands against proteins characterized by high plasticity and multivalent interactions.\n                  <\/jats:p>","DOI":"10.1002\/chem.71218","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T03:46:18Z","timestamp":1780458378000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["De Novo Design of Multivalent \u03b1\/\u03b2\u2010Peptides Mimicking Transcription Factors Targeting the CBP KIX Domain"],"prefix":"10.1002","volume":"32","author":[{"given":"M\u00e1rk V.","family":"Treszti\u00e1n","sequence":"first","affiliation":[{"name":"Department of Medical Chemistry University of Szeged  Szeged Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vencel L.","family":"Petrovicz","sequence":"additional","affiliation":[{"name":"Department 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