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In these analogues, the labile glycosidic and pyrophosphate linkages of UDP-Gal are replaced by chemically and enzymatically stable motifs, yielding compounds that retain key structural features essential for biological recognition. This work demonstrates the first successful nucleophilic substitution of a secondary triflate with a difluoromethylene bisphosphonate, providing a methodology that should enable efficient access to a range of sugar nucleotide mimics. The CH2 and CF2 UDP-Gal analogues 5 and 6 inhibited A4GALT, displaying IC50 values of 249 and 217 \u03bcM, respectively, in the presence of 500 \u03bcM UDP-Gal, consistent with efficient recognition by the A4GALT donor-binding site.<\/jats:p>","DOI":"10.1021\/acs.orglett.6c03808","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T22:01:48Z","timestamp":1790978508000},"page":"12965-12970","source":"Crossref","is-referenced-by-count":0,"title":["Uridine Bisphosphonate-Carbagalactose:\nA Stabilized\n\u03b1-1,4-Galactosyltransferase Inhibitor"],"prefix":"10.1021","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9252-7515","authenticated-orcid":true,"given":"Jianyun","family":"Guo","sequence":"first","affiliation":[{"name":"Leiden University , , Einsteinweg 55 , ,","place":["Leiden, Netherlands, 2333 CC"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicky","family":"de Koster","sequence":"additional","affiliation":[{"name":"Leiden University , , Einsteinweg 55 , ,","place":["Leiden, Netherlands, 2333 CC"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bob","family":"van Puffelen","sequence":"additional","affiliation":[{"name":"Leiden University , , Einsteinweg 55 , ,","place":["Leiden, Netherlands, 2333 CC"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy","family":"Steneker","sequence":"additional","affiliation":[{"name":"Leiden University , , Einsteinweg 55 , ,","place":["Leiden, Netherlands, 2333 CC"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4144-0619","authenticated-orcid":true,"given":"Vincent","family":"Verhoeks","sequence":"additional","affiliation":[{"name":"Leiden University , , Einsteinweg 55 , ,","place":["Leiden, Netherlands, 2333 CC"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim P.","family":"Ofman","sequence":"additional","affiliation":[{"name":"Leiden University , , Einsteinweg 55 , ,","place":["Leiden, Netherlands, 2333 CC"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6976-7005","authenticated-orcid":true,"given":"Herman S.","family":"Overkleeft","sequence":"additional","affiliation":[{"name":"Leiden University , , Einsteinweg 55 , ,","place":["Leiden, Netherlands, 2333 CC"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3051-3902","authenticated-orcid":true,"given":"Marta","family":"Artola","sequence":"additional","affiliation":[{"name":"Leiden University , , Einsteinweg 55 , ,","place":["Leiden, Netherlands, 2333 CC"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitri V.","family":"Filippov","sequence":"additional","affiliation":[{"name":"Leiden University , , Einsteinweg 55 , ,","place":["Leiden, Netherlands, 2333 CC"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3531-2138","authenticated-orcid":true,"given":"Jeroen D. C.","family":"Code\u0301e","sequence":"additional","affiliation":[{"name":"Leiden University , , Einsteinweg 55 , ,","place":["Leiden, Netherlands, 2333 CC"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,2]]},"reference":[{"key":"2026101608471680300_cit1a","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1146\/annurev.biochem.76.061005.092322","article-title":"Glycosyltransferases:\nstructures, functions, and mechanisms","volume":"77","author":"Lairson","year":"2008","journal-title":"Annu.\nRev. 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Drug Des."},{"key":"2026101608471680300_cit19b","doi-asserted-by":"publisher","first-page":"2533","DOI":"10.1021\/jm970247f","article-title":"Synthesis\nof nonhydrolyzable analogues of thiazole-4-carboxamide and benzamide\nadenine dinucleotide containing fluorine atom at the C2\u2019 of\nadenine nucleoside: induction of K562 differentiation and inosine\nmonophosphate dehydrogenase inhibitory activity","volume":"40","author":"Lesiak","year":"1997","journal-title":"J. Med. Chem."},{"key":"2026101608471680300_cit20a","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1021\/ol006422v","article-title":"Synthesis and stereochemical\nelucidation of a 14-membered ring phosphonate","volume":"3","author":"Pungente","year":"2001","journal-title":"Org. 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