ao9b00008_si_001.pdf (4.64 MB)
Synthesis, Derivatization, and Structural Analysis of Phosphorylated Mono‑, Di‑, and Trifluorinated d‑Gluco-heptuloses by Glucokinase: Tunable Phosphoglucomutase Inhibition
journal contribution
posted on 2019-04-18, 15:15 authored by Jian-She Zhu, Kyle M. Stiers, Sherany M. Winter, Anthony D. Garcia, Antoine F. Versini, Lesa J. Beamer, David L. JakemanGlucokinase phosphorylated
a series of C-1 fluorinated α-d-gluco-heptuloses. These
phosphorylated products were discovered
to be inhibitors of α-phosphomannomutase/phosphoglucomutase
(αPMM/PGM) and β-phosphoglucomutase (βPGM). Inhibition
potency with both mutases inversely correlated to the degree of fluorination.
Structural analysis with αPMM demonstrated the inhibitor binding
to the active site, with the phosphate in the phosphate binding site
and the anomeric hydroxyl directed to the catalytic site.