{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T08:13:06Z","timestamp":1788509586367,"version":"build-2803163510"},"reference-count":35,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"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":["Macromol. Rapid Commun."],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Bioconjugates are compounds synthesized by covalently linking biomolecules with a functional fragment, forming a broad class of systems that encompasses pharmaceuticals, molecular probes, and macromolecular materials such as bioconjugated polymers. Achieving such covalent linkage requires the introduction of suitable functional groups for ligation into each fragment. Herein, we report the development of an orthogonal agent as a novel molecular ligation tool that integrates an oxime functionality, which serves as a precursor of a nitrile\n                    <jats:italic>N<\/jats:italic>\n                    \u2010oxide, together with a blocked isocyanate functionality. Treatment of the orthogonal agent with iodosobenzene (PhIO) generates a nitrile\n                    <jats:italic>N<\/jats:italic>\n                    \u2010oxide, which undergoes a catalyst\u2010free [3+2] cycloaddition reaction to an alkene\u2010containing molecule. Subsequent thermal treatment at approximately 120\u00b0C produces an isocyanate that reacts with a nucleophilic molecule without the need for a catalyst, enabling sequential chemical ligation between alkenes and nucleophiles. We further demonstrate the utility of this orthogonal agent through the preparation of biotin\u2010conjugated poly(styrene\u2010\n                    <jats:italic>co<\/jats:italic>\n                    \u2010butadiene) (SB) resin. The polymer structure was characterized by\n                    <jats:sup>1<\/jats:sup>\n                    H NMR and IR spectroscopy, along with a colorimetric assay using horseradish peroxidase (HRP)\u2010conjugated streptavidin. These results highlight that the present orthogonal agent is a versatile and effective ligation tool for catalyst\u2010free bioconjugation of alkene\u2010containing common polymers with biomolecules.\n                  <\/jats:p>","DOI":"10.1002\/marc.70372","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T04:25:23Z","timestamp":1784607923000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Catalyst\u2010Free Biotin Conjugation Onto Poly(Styrene\u2010\n                    <i>co<\/i>\n                    \u2010Butadiene) Mediated by an Orthogonal Agent Comprising Nitrile\n                    <i>N<\/i>\n                    \u2010Oxide and Blocked Isocyanate"],"prefix":"10.1002","volume":"47","author":[{"given":"Sota","family":"Nozawa","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Engineering Toyama Prefectural University  Imizu Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumitake","family":"Usui\u2010Kawanishi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering Toyama Prefectural University  Imizu Toyama Japan"},{"name":"Biotechnology Research Center Toyama Prefectural University  Imizu Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering Toyama Prefectural University  Imizu Toyama Japan"},{"name":"Biotechnology Research Center Toyama Prefectural University  Imizu Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6985-4499","authenticated-orcid":false,"given":"Yasuhito","family":"Koyama","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering Toyama Prefectural University  Imizu Toyama Japan"},{"name":"Biotechnology Research Center Toyama Prefectural University  Imizu Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200801313"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3CS00715D"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-025-01704-3"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja504390x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010chembioeng\u2010092319\u2010083243"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.5b00247"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/1521-3773(20010601)40:11<2004::AID-ANIE2004>3.0.CO;2-5"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/med.20107"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/pol.20210126"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202313063"},{"key":"e_1_2_8_12_1","first-page":"9683","article-title":"Polymeric \u201cClickase\u201d Accelerates the Copper Click Reaction of Small Molecules, Proteins, and Cells","volume":"141","author":"Chen J.","year":"2019","journal-title":"Journal of the American Chemical Society"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202308491"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.4c17615"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.4c02173"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo011148j"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0707090104"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1155106"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja100014q"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja105066t"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1039\/C6RA25633C"},{"key":"e_1_2_8_22_1","first-page":"1","volume-title":"Nitrile Oxides, Nitrones, and Nitronates in Organic Synthesis","author":"Belen'kii L. 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