Pavão M S, Mourão P A, Mulloy B, Tollefsen D M
Departamento de Bioquímica, Universidade Federal do Rio de Janeiro, Brazil.
J Biol Chem. 1995 Dec 29;270(52):31027-36. doi: 10.1074/jbc.270.52.31027.
A dermatan sulfate, similar to the mammalian glycosaminoglycans but not identical with any of them, has been isolated from the body of the ascidian Ascidia nigra. Degradation with chondroitin ABC lyase, analysis of the disaccharide products by digestion with chondro-4- and -6-sulfatases, and 1H and 13C NMR data confirm that the predominant structure is [4-alpha-L-IdoA-(2SO4)-1-->3-beta-D-GalNAc(6SO4)-1]n. Mammalian dermatan sulfate is an anticoagulant due to its ability to potentiate inhibition of thrombin by heparin cofactor II. The structure in dermatan sulfate which binds to heparin cofactor II is [4-alpha-L-IdoA-(2SO4)-1-->3-beta-D-GalNAc(4SO4)-1]n, where n > or = 3. We have compared the ascidian dermatan sulfate with mammalian dermatan sulfate and with chemically oversulfated mammalian dermatan sulfate for anticoagulant activity as measured by the activated partial thromboplastin time assay and for its ability to potentiate heparin cofactor II. In spite of its high content of 2-O-sulfated alpha-L-iduronic acid residues, the ascidian compound had no discernible anticoagulant activity and had low ability to potentiate heparin cofactor II. These results suggest that 4-O-sulfation of the N-acetyl-beta-D-galactosamine residues is essential for the anticoagulant activity of dermatan sulfate.
从黑海鞘的体内分离出了一种硫酸皮肤素，它与哺乳动物的糖胺聚糖相似，但又与其中任何一种都不完全相同。用软骨素ABC裂解酶降解，通过软骨素4-硫酸酯酶和6-硫酸酯酶消化分析二糖产物，以及1H和13C核磁共振数据证实，其主要结构为[4-α-L-艾杜糖醛酸-(2-硫酸酯)-1→3-β-D-氨基半乳糖(6-硫酸酯)-1]n。哺乳动物硫酸皮肤素具有抗凝血作用，因为它能够增强肝素辅因子II对凝血酶的抑制作用。硫酸皮肤素中与肝素辅因子II结合的结构是[4-α-L-艾杜糖醛酸-(2-硫酸酯)-1→3-β-D-氨基半乳糖(4-硫酸酯)-1]n，其中n≥3。我们将海鞘硫酸皮肤素与哺乳动物硫酸皮肤素以及化学过硫酸化的哺乳动物硫酸皮肤素进行了比较，通过活化部分凝血活酶时间测定法测量其抗凝血活性，并比较其增强肝素辅因子II的能力。尽管海鞘化合物中2-O-硫酸化的α-L-艾杜糖醛酸残基含量很高，但它没有明显的抗凝血活性，增强肝素辅因子II的能力也很低。这些结果表明，N-乙酰-β-D-半乳糖胺残基的4-O-硫酸化对于硫酸皮肤素的抗凝血活性至关重要。
