Chondroitin Sulfate Clinical Study

Deepa SS, Yamada S, Fukui S, Sugahara K.

Department of Biochemistry, Kobe Pharmaceutical University, Higashinada-ku, Kobe 658-8558, Japan.

Twelve octasaccharide fractions were obtained from chondroitin sulfate C derived from shark cartilage after hyaluronidase digestion. Their sugar and sulfate composition was assigned by MALDI-TOF/MS. The sequences were determined at low picomole amounts by a combination of enzymatic digestions with HPLC, and were composed of disaccharide building units including O [GlcUAb1-3GalNAc], C [GlcUAb1-3GalNAc(6S)], A [GlcUAb1-3GalNAc(4S)] and/or D [GlcUA(2S)b1-3GalNAc(6S)], where 2S, 4S and 6S represent 2-O-, 4-O- and 6-O-sulfate, respectively. As many as 24 different sequences including minor ones were revealed, exhibiting a high degree of structural diversity reflecting the enormous heterogeneity of the parent polysaccharides. Nineteen of them were novel, with the other four reported previously as unsaturated counterparts obtained after digestion with chondroitinase. A microarray of these structurally defined octasaccharide fractions were prepared using low picomole amounts of their lipid-derivatives to investigate the binding specificity of four commercial anti-chondroitin sulfate antibodies CS-56, MO-225, 2H6 and LY111. The results revealed that multiple unique sequences were recognized by each antibody, which implies that the common conformation shared by the multiple primary sequences in the intact CS chains is important as an epitope for each mAb. Comparison of the specificity of the tested antibodies indicates that CS-56 and MO-225 specifically recognize octasaccharides containing an A-D tetrasaccharide sequence, whereas 2H6 and LY111 require a hexasaccharide as a minimum size for their binding, and prefer sequences with A- and C-units such as C-C-A-C (2H6) or C-C-A-O, C-C-A-A and C-C-A-C (LY111) for strong binding but require no D-unit.

PMID: 17317718 [PubMed - as supplied by publisher]

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