@article { ISI:000176472200018, title = {Synthesis and evaluation of potential inhibitors of chondroitin AC lyase from Flavobacterium heparinum}, journal = {JOURNAL OF ORGANIC CHEMISTRY}, volume = {67}, number = {13}, year = {2002}, month = {JUN 28}, pages = {4505-4512}, abstract = {Chondroitin AC lyase from Flavobacterium heparinum degrades chondroitin sulfate glycosamino-glycans via an elimination mechanism, resulting in disaccharides or oligosaccharides with Delta4,5-unsaturated uronic acid residues at their nonreducing end. The syntheses and testing of two potential inhibitors of this lyase are described. Methyl O-(2-acetamido-2-deoxy-beta-D-galactopyranosyl)(1{\textendash}>4)-alpha-L-threo-hex -4-enopyranoside, 1, has the trigonal geometry at C5 of the uronic acid moiety expected at the transition state, yet retains the {\textquoteleft}{\textquoteleft}leaving group{{\textquoteright}{\textquoteright}} sugar moiety. Surprisingly, compound 1 showed no inhibition of the enzyme. The novel 5-nitro sugar, phenyl (5S)-5-nitro-beta-D-xylopyranoside, 2, is a monosaccharide nitro analogue of the natural substrate, with C5 being a carbon acid of pK(a) 8.8. The rate of reprotonation of the anion generated at this center is sufficiently low that the anion of 2 can be used directly in initial steady-state velocity measurements without significant interference from the conjugate carbon acid. The anion of compound 2 was found to be a competitive inhibitor with a K-i value of 5 mM, whereas the conjugate acid had a K-i value of 35 mM.}, issn = {0022-3263}, doi = {10.1021/jo020089m}, author = {Rye, CS and Withers, SG} }