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PEGylation is one possible strategy to improve the solubility of the drug, however, means to cleave off the PEG after reaching the target is important to make use of the therapeutic effects of the native drug. Moreover, the length of the PEG chains will have an effect on the solubility and binding. In this study, we want to extend our understanding of solubilizing oligo ethylene glycol (OEG) chains connected to kinase inhibitors using a pH labile phosphoramidate linker. We synthesize a library of drug\u2010OEG conjugates for Ceritinib, Crizotinib, Palbociclib, and Ribocilib kinase inhibitors with n=2, 3, 4 and 8 OEG repeat units. We study the influence on water solubility, enzyme inhibition, and pH induced hydrolysis. A maximum in solubility is obtained for n=3 or 4. We show that small differences in chain length can strongly influence the water solubility, while all other properties remain relatively comparable.<\/jats:p>","DOI":"10.1002\/chem.202404618","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T06:41:23Z","timestamp":1737009683000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Oligoethylene Phosphoramidate\u2010Based Kinase Inhibitor Prodrugs \u2013 Solubility, Enzyme Inhibition, and Hydrolysis"],"prefix":"10.1002","volume":"31","author":[{"given":"Sarah","family":"Spiewok","sequence":"first","affiliation":[{"name":"Institute of Organic and Macromolecular Chemistry Ulm University  Albert-Einstein-Allee 11 89081 Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Schaefer","sequence":"additional","affiliation":[{"name":"Institute of Organic and Macromolecular Chemistry Ulm University  Albert-Einstein-Allee 11 89081 Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Lamla","sequence":"additional","affiliation":[{"name":"Institute of Organic and Macromolecular Chemistry Ulm University  Albert-Einstein-Allee 11 89081 Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yannick","family":"Jaritz","sequence":"additional","affiliation":[{"name":"Institute of Organic and Macromolecular Chemistry Ulm University  Albert-Einstein-Allee 11 89081 Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0142-8001","authenticated-orcid":false,"given":"Alexander J. 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