{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T03:57:09Z","timestamp":1790567829415,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"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":["ChemMedChem"],"published-print":{"date-parts":[[2026,9,28]]},"abstract":"<jats:p>Ribonuclease\u2010targeting chimeras (RIBOTACs) are heterobifunctional molecules composed of an RNA\u2010binding motif and an RNase L\u2013recruiting module, enabling selective RNA cleavage by recruited RNase L. While optimization efforts have primarily focused on RNA\u2010binding ligands and RNase L\u2010recruiting motifs, the linker design remains poorly understood. Here, we systematically evaluated the impact of linker length and rigidity in a cMYC\u2010targeting RIBOTAC system. A series of PEG\u2010based linkers (PEG2\u2013PEG7) was employed while maintaining identical RNA\u2010binding and RNase L\u2013recruiting modules. Functional evaluation through in vitro cleavage, RT\u2010qPCR, and Western blot analysis established PEG3 and PEG4 as the optimal linkers, whereas further elongation to PEG5\u20107 or substitution with a rigid triazole\u2010based linker resulted in complete loss of activity. These findings demonstrate that precise linker design is essential for effective RNA degradation.<\/jats:p>","DOI":"10.1002\/cmdc.70495","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T06:17:15Z","timestamp":1789539435000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Linker Optimization of cMYC RIBOTAC for Efficient cMYC Modulation"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0013-9512","authenticated-orcid":false,"given":"Sivakumar","family":"Komachankandy","sequence":"first","affiliation":[{"name":"Department of Chemistry Pusan National University  Busan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7481-9839","authenticated-orcid":false,"given":"Jinseo","family":"Heo","sequence":"additional","affiliation":[{"name":"Department of Chemistry Pusan National University 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