| Abstract
| - Chondroitin AC lyase from Flavobacterium heparinum degrades chondroitin sulfate glycosaminoglycans via an elimination mechanism, resulting in disaccharides or oligosaccharides with Δ4,5-unsaturated uronic acid residues at their nonreducing end. The syntheses and testing of twopotential inhibitors of this lyase are described. Methyl O-(2-acetamido-2-deoxy-β-d-galactopyranosyl)-(1→4)-α-l-threo-hex-4-enopyranoside, 1, has the trigonal geometry at C5 of the uronic acid moietyexpected at the transition state, yet retains the “leaving group” sugar moiety. Surprisingly,compound 1 showed no inhibition of the enzyme. The novel 5-nitro sugar, phenyl (5S)-5-nitro-β-d-xylopyranoside, 2, is a monosaccharide nitro analogue of the natural substrate, with C5 being acarbon acid of pKa 8.8. The rate of reprotonation of the anion generated at this center is sufficientlylow that the anion of 2 can be used directly in initial steady-state velocity measurements withoutsignificant interference from the conjugate carbon acid. The anion of compound 2 was found to bea competitive inhibitor with a Ki value of 5 mM, whereas the conjugate acid had a Ki value of 35mM.
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