{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T16:14:09Z","timestamp":1783786449300,"version":"3.55.0"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T00:00:00Z","timestamp":1741824000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Japan Society for the Promotion of Science (JSPS) KAKENHI","award":["JP22K05335"],"award-info":[{"award-number":["JP22K05335"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Calreticulin (CRT), a chaperone that possesses both lectin and chaperone domains, is localized in the endoplasmic reticulum (ER). CRT has diverse functions and localizations; thus, CRT is a multifunctional protein. Particularly in the ER, CRT mainly aids in the proper folding of nascent glycoproteins as lectin chaperones. Approximately one-third of cellular proteins, including disease-related proteins, are synthesized in the ER. The lectin chaperones CRT and calnexin facilitate the correct folding of these glycoproteins; hence, these chaperones are essential for cells. Various CRT ligands have been reported, mainly composed of Glc1Man9GlcNAc2-type glycan. However, it remains problematic for the complicated synthesis and preparation, and it interacts with glycoprotein folding-related proteins in the ER other than CRT. This suggests that the development of CRT ligands still can be improved. In this study, we developed a hybrid binding concept, which encompasses concurrent binding of ligands to CRT lectin and chaperone domains. We synthesized a CRT-targeting glycan ligand with a glycan and hydrophobic aglycone for CRT lectin and chaperone domain binding, respectively. The thermal shift assay with the CRT-targeting glycan demonstrated that binding was enhanced by simultaneous glycan and hydrophobic aglycone binding. The affinity of the CRT-targeting ligand showed isothermal titration calorimetry approximately 50-fold stronger than that of the glycan alone, thereby supporting the hybrid binding concept. In addition, the CRT-targeting ligand inhibited chaperone function. Overall, these results indicate that the hybrid binding concept may be useful as a novel strategy for the development of CRT ligands and inhibitors.<\/jats:p>","DOI":"10.1093\/glycob\/cwaf015","type":"journal-article","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T08:59:41Z","timestamp":1741856381000},"source":"Crossref","is-referenced-by-count":4,"title":["Development of a Calreticulin-targeting Glycan Ligand Based on a Hybrid Binding Concept"],"prefix":"10.1093","author":[{"given":"Taiki","family":"Kuribara","sequence":"first","affiliation":[{"name":"Department of Science and Technology, Seikei University , Tokyo 180-8633 ,","place":["Japan"]},{"name":"Department of Glyco-Oncology and Medical Biochemistry, Research Institute, Osaka International Cancer Institute , Osaka 541-8567 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiga","family":"Kojima","sequence":"additional","affiliation":[{"name":"Department of Science and Technology, Seikei University , Tokyo 180-8633 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Science and Technology, Seikei University , Tokyo 180-8633 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuaki","family":"Hirose","sequence":"additional","affiliation":[{"name":"Department of Science and Technology, Seikei University , Tokyo 180-8633 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keita","family":"Shibayama","sequence":"additional","affiliation":[{"name":"Department of Science and Technology, Seikei University , Tokyo 180-8633 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichi","family":"Takeda","sequence":"additional","affiliation":[{"name":"Graduate School of Life Sciences, Ritsumeikan University , Kusatsu, Shiga 525-8577 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4957-1686","authenticated-orcid":false,"given":"Kiichiro","family":"Totani","sequence":"additional","affiliation":[{"name":"Department of Science and Technology, Seikei University , Tokyo 180-8633 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,3,13]]},"container-title":["Glycobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/glycob\/advance-article-pdf\/doi\/10.1093\/glycob\/cwaf015\/62397854\/cwaf015.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/glycob\/advance-article-pdf\/doi\/10.1093\/glycob\/cwaf015\/62397854\/cwaf015.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T08:59:44Z","timestamp":1741856384000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/glycob\/advance-article\/doi\/10.1093\/glycob\/cwaf015\/8074745"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,13]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1093\/glycob\/cwaf015","relation":{},"ISSN":["1460-2423"],"issn-type":[{"value":"1460-2423","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,13]]},"article-number":"cwaf015"}}