Uridine Bisphosphonate-Carbagalactose: A Stabilized α-1,4-Galactosyltransferase Inhibitor.
- 1Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CCLeiden, Netherlands.
Abstract
Methylene and difluoromethylene uridine bisphosphonate carbagalactose were designed and synthesized as stable uridine diphosphate-galactose (UDP-Gal) mimics for probing α-1,4-galactosyltransferase (A4GALT). 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 μM, respectively, in the presence of 500 μM UDP-Gal, consistent with efficient recognition by the A4GALT donor-binding site.
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BibTeX
@article{guo2026uridine,
title = {{Uridine Bisphosphonate-Carbagalactose: A Stabilized α-1,4-Galactosyltransferase Inhibitor.}},
author = {Jianyun Guo and Nicky de Koster and Bob van Puffelen and Roy Steneker and Vincent Verhoeks and Tim P Ofman and Herman S Overkleeft and Marta Artola and Dmitri V Filippov and Jeroen D C Codée},
journal = {Organic letters},
year = {2026},
month = oct,
doi = {10.1021/acs.orglett.6c03808},
url = {https://europepmc.org/article/MED/42917714},
note = {CC BY},
}
RIS
TY - JOUR
TI - Uridine Bisphosphonate-Carbagalactose: A Stabilized α-1,4-Galactosyltransferase Inhibitor.
AU - Jianyun Guo
AU - Nicky de Koster
AU - Bob van Puffelen
AU - Roy Steneker
AU - Vincent Verhoeks
AU - Tim P Ofman
AU - Herman S Overkleeft
AU - Marta Artola
AU - Dmitri V Filippov
AU - Jeroen D C Codée
PY - 2026
DA - 2026/10/01
JO - Organic letters
DO - 10.1021/acs.orglett.6c03808
UR - https://europepmc.org/article/MED/42917714
AB - Methylene and difluoromethylene uridine bisphosphonate carbagalactose were designed and synthesized as stable uridine diphosphate-galactose (UDP-Gal) mimics for probing α-1,4-galactosyltransferase (A4GALT). 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 μM, respectively, in the presence of 500 μM UDP-Gal, consistent with efficient recognition by the A4GALT donor-binding site.
SN - 1523-7060
SN - 1523-7052
ER -