@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}
}
