Structural analysis of two 2-deoxy analogues of alpha- and beta-KDO and the methyl alpha- and beta-glycosides of KDO, and determination of their metal-ion-binding properties.
Ammonium 2,6-anhydro-3-deoxy-D-glycero-D-talo-octonate (1), a potent inhibitor of the enzyme CMP-KDO synthetase, its C-2 epimer 2, and the methyl beta- (3) and alpha-glycoside (4) of KDO were studied by 1H- and 13C-n.m.r. spectroscopy. Compound 1 was also analysed by X-ray crystallography. Each compound adopted a 5C2 chair conformation with the side chain equatorial. The preponderant side-chain conformation of 1 in solution was the same as that in the crystal and was stabilised by an intramolecular hydrogen bond from HO-8 to the carboxylate group. This hydrogen bond appeared to be present also in 3. However, the side-chain conformation of 2 and 4 was different from that in 1 and 3. The metal-ion-binding properties, determined on the basis of the line-broadening effects of Mn2+ on the 13C-n.m.r. signals, showed that the carboxylate group was involved in the binding with O-8 in 1 and 3 and with O-6 and O-8 in 2 and 4.
Luthman
K
K
Department of Organic Pharmaceutical Chemistry, Uppsala Biomedical Center, Uppsala University, Sweden.
Claesson
A
A
Kenne
L
L
Csöregh
I
I
D002236:Carbohydrate Conformation; D006027:Glycosides; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009713:Nucleotidyltransferases / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D013400:Sugar Acids; D013816:Thermodynamics; D014961:X-Ray Diffraction
D006027:Glycosides; D013400:Sugar Acids; C002532:2-keto-3-deoxyoctonate; D009713:Nucleotidyltransferases; C028984:3-deoxy-manno-octulosonate cytidyltransferase