Pol-Fachin Laercio, Verli Hugo
Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Av Bento Gonçalves 9500, CP 15005, Porto Alegre 91500-970, RS, Brazil.
Carbohydr Res. 2008 Jul 7;343(9):1435-45. doi: 10.1016/j.carres.2008.04.016. Epub 2008 Apr 22.
2-O-Sulfo-alpha-l-iduronic acid (IdoA2S) is one of the main components of heparin, an anticoagulant and antithrombotic polysaccharide able to potentiate the inhibitory effect of antithrombin over plasma serine proteases. This monosaccharide unit adopts an equilibrium between chair (1C4) and skew-boat (2SO) forms as a function of heparin sequence size and composition. Although the prevalence of the 1C4 chair conformation in monosaccharides is understood, the reasons for the increase in 2SO contribution in the whole polysaccharide chain are still uncertain. In this context, 0.2 mus molecular dynamics simulations of IdoA2S-containing oligosaccharides indicated that stabilization due to intramolecular hydrogen bonds around IdoA2S is highly correlated (p0.001) with the expected conformational equilibrium for this residue in solution. This behavior explains the known effect of different heparin compositions, at the monosaccharide level, on IdoA2S conformation in biological solutions.
2-O-磺基-α-L-艾杜糖醛酸（艾杜糖醛酸2-O-硫酸酯，IdoA2S）是肝素的主要成分之一，肝素是一种抗凝和抗血栓多糖，能够增强抗凝血酶对血浆丝氨酸蛋白酶的抑制作用。这种单糖单元根据肝素序列的大小和组成，在椅式（1C4）和扭船式（2SO）构象之间达到平衡。虽然单糖中1C4椅式构象的优势已为人所知，但在整个多糖链中2SO构象比例增加的原因仍不明确。在此背景下，对含IdoA2S的寡糖进行的0.2微秒分子动力学模拟表明，IdoA2S周围分子内氢键导致的稳定作用与该残基在溶液中的预期构象平衡高度相关（p<0.001）。这种行为解释了在单糖水平上，不同肝素组成对生物溶液中IdoA2S构象的已知影响。
