Venkataraman G, Sasisekharan V, Cooney C L, Langer R, Sasisekharan R
Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Cambridge 02139.
Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):6171-5. doi: 10.1073/pnas.91.13.6171.
Glycosaminoglycans, such as heparin, heparan sulfate, and dermatan sulfate, are characterized by a disaccharide repeating unit of a uronate and a hexosamine and are increasingly understood to be important physiologically as soluble components of the extracellular matrix. The secondary structure of this class of acidic polysaccharides is believed to play a key role in determining the wide range of biological specificities. Central to the structural diversity of the glycosaminoglycans is the experimentally documented conformational flexibility of the iduronate residue. Here, we outline an approach to explore the iduronate conformational flexibility by imposing stereochemical criteria of nonbonded contact distances. By performing a complete search of all possible torsions that define the iduronate ring geometry, we eliminate any prior bias with regard to minimum energy conformers. The approach led to alternative feasible conformers for the iduronate ring that are stereochemically satisfactory and are consistent with the available physico-chemical data.
糖胺聚糖，如肝素、硫酸乙酰肝素和硫酸皮肤素，其特征在于由糖醛酸和己糖胺组成的二糖重复单元，并且越来越被认为是细胞外基质的可溶性成分，在生理上具有重要意义。这类酸性多糖的二级结构被认为在决定广泛的生物学特异性方面起着关键作用。糖胺聚糖结构多样性的核心是实验证明的艾杜糖醛酸残基的构象灵活性。在这里，我们概述了一种通过施加非键接触距离的立体化学标准来探索艾杜糖醛酸构象灵活性的方法。通过对定义艾杜糖醛酸环几何形状的所有可能扭转进行全面搜索，我们消除了对最低能量构象体的任何先验偏见。该方法产生了艾杜糖醛酸环的替代可行构象体，这些构象体在立体化学上是令人满意的，并且与现有的物理化学数据一致。
