{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T17:05:11Z","timestamp":1784394311178,"version":"3.55.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Fab has been extensively studied to elucidate the structural and physicochemical principles underlying antigen recognition. While most investigations have focused on IgG-derived Fabs, comparatively little is known about those from other isotypes. To investigate the role of the IgM constant domain C\u03bc1, we engineered a chimeric Fab (C\u03bc1Fab) in which the CH1 domain of adalimumab Fab (IgG1) was replaced by the human IgM C\u03bc1 domain. C\u03bc1Fab was expressed in CHO cells and its physicochemical properties were evaluated. SDS-PAGE analysis with or without PNGase F treatment demonstrated that the N166\u2013N167\u2013S168 motif was N-glycosylated. SPR analysis demonstrated that C\u03bc1Fab retained antigen-binding activity comparable to that of the wild-type Fab, and elimination of the glycosylation motif (N166A) did not alter binding affinity. Notably, N-linked glycosylation within the C\u03bc1 domain suppressed aggregation, whereas the N166A variant showed marked aggregation. DSC further revealed that the glycosylation affected thermal stability. The melting temperature (Tm) of the N166A variant was 60.5\u00b0C, substantially lower than that of the C\u03bc1Fab (Tm\u2009=\u200966.0\u00b0C), although Tm of the wild-type Fab was 75.2\u00b0C. Collectively, these findings establish the critical role of native C\u03bc1 N-linked glycosylation in Fab stability, offering new insights for antibody engineering.<\/jats:p>","DOI":"10.1093\/jb\/mvag008","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T12:22:11Z","timestamp":1770034931000},"page":"341-349","source":"Crossref","is-referenced-by-count":1,"title":["Chimeric Fab incorporating the IgM C\u03bc1 domain: insights into physicochemical properties"],"prefix":"10.1093","volume":"179","author":[{"given":"Rara","family":"Sugimoto","sequence":"first","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Sojo University , 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0082 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5969-8138","authenticated-orcid":false,"given":"Masato","family":"Kiyoshi","sequence":"additional","affiliation":[{"name":"Division of Biological Chemistry and Biologicals, National Institute of Health Sciences , 3-25-26, Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-9501 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitomi","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Sojo University , 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0082 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Oda-Ueda","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Sojo University , 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0082 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Ishii-Watabe","sequence":"additional","affiliation":[{"name":"Division of Biological Chemistry and Biologicals, National Institute of Health Sciences , 3-25-26, Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-9501 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0685-3330","authenticated-orcid":false,"given":"Takatoshi","family":"Ohkuri","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Sojo University , 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0082 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,2,5]]},"reference":[{"key":"2026042705171111500_ref1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.4161\/19420862.2015.989042","article-title":"The therapeutic monoclonal antibody market","volume":"7","author":"Ecker","year":"2015","journal-title":"MAbs."},{"key":"2026042705171111500_ref2","doi-asserted-by":"crossref","first-page":"2297450","DOI":"10.1080\/19420862.2023.2297450","article-title":"Antibodies to watch in 2024","volume":"16","author":"Crescioli","year":"2024","journal-title":"MAbs."},{"key":"2026042705171111500_ref3","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1007\/s13238-017-0457-8","article-title":"Current progress in innovative engineered antibodies","volume":"9","author":"Strohl","year":"2018","journal-title":"Protein Cell"},{"key":"2026042705171111500_ref4","doi-asserted-by":"crossref","first-page":"403","DOI":"10.4161\/mabs.19909","article-title":"The birth pangs of monoclonal antibody therapeutics: the failure and legacy of Centoxin","volume":"4","author":"Marks","year":"2012","journal-title":"MAbs."},{"key":"2026042705171111500_ref5","doi-asserted-by":"crossref","first-page":"2483","DOI":"10.1158\/1535-7163.MCT-20-1132","article-title":"Multimeric anti-DR5 IgM agonist antibody IGM-8444 is a potent inducer of cancer cell apoptosis and synergizes with chemotherapy and BCL-2 inhibitor ABT-199","volume":"20","author":"Wang","year":"2021","journal-title":"Mol. 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