{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:42:11Z","timestamp":1792460531075,"version":"4.5.0"},"reference-count":59,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T00:00:00Z","timestamp":1736812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T00:00:00Z","timestamp":1736812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2025,2,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Therapeutic proteins are commonly conjugated with polymers to modulate their pharmacokinetics but often lack a description of the polymer\u2010protein interaction. We deployed limited proteolysis mass spectrometry (LiP\u2010MS) to reveal the interaction of polyethylene glycol (PEG) and PEG alternative polymers with interferon\u2010\u03b12a (IFN). Target conjugates were digested with the specific protease trypsin and a \u201cheavy\u201d\n                    <jats:sup>15<\/jats:sup>\n                    N\u2010IFN wild type (IFN\u2010WT) for time\u2010resolved quantification of the cleavage dynamics. Interactions between IFN\u2010\u03b12a and its high\u2010affinity receptor were detailed by LiP\u2010MS. Then, 10\u2005kDa polymers of PEG, linear polyglycerol (LPG), and poly(2\u2010oxazoline) (POX) with two different cyclooctyne linkers (BCN\/DBCO) were used for site\u2010specific bioconjugation to azide functionalized IFN\u2010\u03b12a. Tryptic events at each cleavage site and in different structural environments (loops\/helices) were compared. PEG and LPG were similar, and POX showed a reduced interaction profile with the IFN\u2010\u03b12a surface. All\u2010atom molecular dynamics simulations of IFN\u2010DBCO\u2010polymer conjugates revealed distinct and transient (below 50\u2005ns) protein\u2010interaction profiles for PEG, LPG, and POX. Cleavage dynamics of IFN\u2010polymer conjugates from the BCN handle were homogeneous, pointing to a more conserved IFN structure than DBCO\u2010polymer conjugates. In summary, time\u2010resolved LiP\u2010MS for quantification of cleavage events enhances the structural understanding of transient IFN\u2010polymer interactions, which may be extended to other bioconjugate types.\n                  <\/jats:p>","DOI":"10.1002\/anie.202415354","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T03:58:07Z","timestamp":1736395087000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Deciphering Polymer Interactions in Bioconjugates with Different Architectures by Structural Analysis via Time\u2010Resolved Limited Proteolysis Mass Spectrometry"],"prefix":"10.1002","volume":"64","author":[{"given":"Prisca","family":"Hamm","sequence":"first","affiliation":[{"name":"Universit\u00e4t W\u00fcrzburg Institute for Pharmacy and Food Chemistry  Am Hubland 97074 W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc 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