REGIOSELECTIVITY IN THE SULFATION OF DERMATAN SULFATE AND METHYL 4,6-O-BENZYLIDENE-ALPHA-D-IDOPYRANOSIDE

被引:11
作者
LUDWIGBAXTER, KG
LIU, ZC
PERLIN, AS
机构
[1] Department of Chemistry, McGill University, Montreal
关键词
D O I
10.1016/0008-6215(91)80032-I
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The sulfation of dermatan sulfate by SO3-trimethylamine in N,N-dimethylformamide led to substitution initially at HO-6 of residues of 2-acetamido-2-deoxy-beta-D-galactopyranosyl4-sulfate (1), to produce the 4,6-disulfate (6). When this step reached a level of > 50%, sulfation occurred with equal facility at HO-2 and HO-3 of residues of alpha-L-idopyranosyluronic acid (2), giving rise to a mixture of 2-, 3-, and 2,3-disulfates. An analogous substitution pattern was observed for HO-2 and -3 of a simpler idopyranose unit, in the sulfation of methyl 4,6-O-benzylidene-alpha-D-idopyranoside (12). This lack of regioselectivity in the reaction of 2 (and 12) constrasts markedly with the high affinity of the reagent for HO-3 of residues of alpha-L-idopyranosyluronic acid present in a modified form of heparin. It is attributed to a difference between the two polymers in the relative orientation of their neighboring amino sugar residues, whereby there is an unobstructed access of the reagent in one instance, and hindrance of HO-2 selectively in the other. Enzymolysis by chondroitinase ABC was found to yield unsaturated disaccharide containing residues of 4,6-disulfate, as well as larger fragments containing unsaturated glycosyl groups derived from L-idopyranosyluronic acid 2-sulfate, evidence of a relatively broad enzyme specificity. The presence of extra sulfate groups in dermatan sulfate did not enhance its weak antithrombotic activity, as measured by anti Xa, assay, in disagreement with earlier reports.
引用
收藏
页码:245 / 256
页数:12
相关论文
共 32 条
[1]   CORRELATION OF PROTON CHEMICAL-SHIFTS BY TWO-DIMENSIONAL FOURIER-TRANSFORM NMR [J].
BAX, A ;
FREEMAN, R ;
MORRIS, G .
JOURNAL OF MAGNETIC RESONANCE, 1981, 42 (01) :164-168
[2]   H-1-NMR INVESTIGATION OF NATURALLY-OCCURRING AND CHEMICALLY OVERSULPHATED DERMATAN SULFATES - IDENTIFICATION OF MINOR MONOSACCHARIDE RESIDUES [J].
BOSSENNEC, V ;
PETITOU, M ;
PERLY, B .
BIOCHEMICAL JOURNAL, 1990, 267 (03) :625-630
[3]  
Buck K. W., 1966, CARBOHYD RES, V2, P122
[4]   INFRARED-ABSORPTION AND RAMAN-SCATTERING OF SULFATE GROUPS OF HEPARIN AND RELATED GLYCOSAMINOGLYCANS IN AQUEOUS-SOLUTION [J].
CABASSI, F ;
CASU, B ;
PERLIN, AS .
CARBOHYDRATE RESEARCH, 1978, 63 (JUN) :1-11
[5]   INFRARED-SPECTRA OF GLYCOSAMINOGLYCANS IN DEUTERIUM-OXIDE AND DEUTERIUM CHLORIDE SOLUTION - QUANTITATIVE-EVALUATION OF URONIC-ACID AND ACETAMIDODEOXYHEXOSE MOIETIES [J].
CASU, B ;
SCOVENNA, G ;
CIFONELLI, AJ ;
PERLIN, AS .
CARBOHYDRATE RESEARCH, 1978, 63 (JUN) :13-27
[6]   CONTROVERSIAL GLYCOSAMINO-GLYCAN CONFORMATIONS [J].
CASU, B ;
CHOAY, J ;
FERRO, DR ;
GATTI, G ;
JACQUINET, JC ;
PETITOU, M ;
PROVASOLI, A ;
RAGAZZI, M ;
SINAY, P ;
TORRI, G .
NATURE, 1986, 322 (6076) :215-216
[7]   STUDY OF DISACCHARIDE CONFORMATION BY ONE-DIMENSIONAL AND TWO-DIMENSIONAL NMR-SPECTROSCOPY - 1,6-ANHYDRO-BETA-MALTOSE HEXAACETATE [J].
DAIS, P ;
PERLIN, AS .
MAGNETIC RESONANCE IN CHEMISTRY, 1988, 26 (05) :373-379
[8]   STUDY OF DISACCHARIDE CONFORMATION BY MEASUREMENTS OF NUCLEAR OVERHAUSER ENHANCEMENT, RELAXATION RATES, AND C-13-H-1 COUPLING - 1,6-ANHYDRO-BETA-CELLOBIOSE HEXAACETATE [J].
DAIS, P ;
SHING, TKM ;
PERLIN, AS .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1984, 106 (11) :3082-3089
[10]   ALPHA-L-IDURONATE RING CONFORMATIONS IN HEPARIN AND HEPARIN DERIVATIVES - C-13 NMR ANALYSES AND TITRATION DATA FOR VARIOUSLY DESULFATED AND PERIODATE-OXIDIZED HEPARINS [J].
FRANSSON, LA ;
HUCKERBY, TN ;
NIEDUSZYNSKI, IA .
BIOCHEMICAL JOURNAL, 1978, 175 (01) :299-309