New insights on the specificity of heparin and heparan sulfate lyases fromFlavobacterium heparinum revealed by the use of synthetic derivatives of K5 polysaccharide from E-coli and 2-O-desulfated heparin

Citation
Hb. Nader et al., New insights on the specificity of heparin and heparan sulfate lyases fromFlavobacterium heparinum revealed by the use of synthetic derivatives of K5 polysaccharide from E-coli and 2-O-desulfated heparin, GLYCOCON J, 16(6), 1999, pp. 265-270
Citations number
26
Categorie Soggetti
Biochemistry & Biophysics
Journal title
GLYCOCONJUGATE JOURNAL
ISSN journal
02820080 → ACNP
Volume
16
Issue
6
Year of publication
1999
Pages
265 - 270
Database
ISI
SICI code
0282-0080(199906)16:6<265:NIOTSO>2.0.ZU;2-I
Abstract
The capsular polysaccharide from E. Coli, strain K5 composed of ....--> 4)b eta-D-GlcA(1 --> 4)alpha-D-GlcNAc(1 --> 4)beta-D-GlcA (1 -->....., chemical ly modified K5 polysaccharides, bearing sulfates at C-2 and C-6 of the hexo samine moiety and at the C-2 of the glucuronic acid residues as well as 2-O desulfated heparin were used as substrates to study the specificity of hep aritinases I and II and heparinase from Flavobacterium heparinum. The natur al K5 polysaccharide was susceptible only to heparitinase I forming Delta U -GlcNAc. N-deacetylated, N-sulfated K5 became susceptible to both heparitin ases I and II producing Delta U-GlcNS. The K5 polysaccharides containing su lfate at the C-2 and C-6 positions of the hexosamine moiety and C-2 positio n of the glucuronic acid residues were susceptible only to heparitinase II producing Delta U-GlcNS,6S and Delta U,2S-GlcNS,6S respectively. These comb ined results led to the conclusion that the sulfate at C-6 position of the glucosamine is impeditive for the action of heparitinase I and that heparit inase II requires at least a C-2 or a C-6 sulfate in the glucosamine residu es of the substrate for its activity. Iduronic acid-2-O-desulfated heparin was susceptible only to heparitinase II producing Delta U-GlcNS,6S. All the modified K5 polysaccharides as well as the desulfated heparin were not sub strates for heparinase. This led to the conclusion that heparitinase II act s upon linkages containing non-sulfated iduronic acid residues and that hep arinase requires C-2 sulfated iduronic acid residues for its activity.