Sugar nucleotide recognition by Klebsiella pneumoniae UDP-D-galactopyranose mutase: Fluorinated substrates, kinetics and equilibria

A series of selectively fluorinated and other substituted UDP-D-galactose derivatives have been evaluated as substrates for Klebsiella pneumoniae UDP-D-galactopyranose mutase. This enzyme, which catalyses the interconversion of the pyranose and furanose forms of galactose as its UDP adduct, is a prospective drug target for a variety of microbial infections. We show that none of the 2 ''-, 3 ''-or 6 ''-hydroxyl groups of UDP-D-galactopyranose are essential for substrate binding and turnover. However, steric factors appear to play an important role in limiting the range of substitutions that can be accommodated at C-2 '' and C-6 '' of the sugar nucleotide substrate. Attempts to invert the C-2 '' stereochemistry from equatorial to axial, changing D-galacto-to D-talo-configuration, in an attempt to exploit the higher percentage of furanose at equilibrium in the talo-series, met with no turnover of substrate.</p

Among sadists

In the decade after the death of Edmund Campion at Tyburn on December 1, 1581, his fellow Jesuit Robert Southwell composed extraordinary verses which were circulated in secret manuscript and...</p