Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute , Troy, New York 12180, United States.
Anal Chem. 2016 Jul 5;88(13):6648-52. doi: 10.1021/acs.analchem.6b01662. Epub 2016 Jun 15.
Heparan sulfate (HS) polysaccharides are ubiquitous in animal tissues as components of proteoglycans, and they participate in many important biological processes. HS carbohydrate chains are complex and can contain rare structural components such as N-unsubstituted glucosamine (GlcN). Commercially available HS preparations have been invaluable in many types of research activities. In the course of preparing microarrays to include probes derived from HS oligosaccharides, we found an unusually high content of GlcN residue in a recently purchased batch of porcine intestinal mucosal HS. Composition and sequence analysis by mass spectrometry of the oligosaccharides obtained after heparin lyase III digestion of the polysaccharide indicated two and three GlcN in the tetrasaccharide and hexasaccharide fractions, respectively. (1)H NMR of the intact polysaccharide showed that this unusual batch differed strikingly from other HS preparations obtained from bovine kidney and porcine intestine. The very high content of GlcN (30%) and low content of GlcNAc (4.2%) determined by disaccharide composition analysis indicated that N-deacetylation and/or N-desulfation may have taken place. HS is widely used by the scientific community to investigate HS structures and activities. Great care has to be taken in drawing conclusions from investigations of structural features of HS and specificities of HS interaction with proteins when commercial HS is used without further analysis. Pending the availability of a validated commercial HS reference preparation, our data may be useful to members of the scientific community who have used the present preparation in their studies.
硫酸乙酰肝素(HS)多糖作为蛋白聚糖的成分存在于动物组织中,参与许多重要的生物学过程。HS 糖链结构复杂,可包含罕见的结构成分,如 N-未取代的葡萄糖胺(GlcN)。商业上可获得的 HS 制剂在许多类型的研究活动中非常有价值。在制备包含 HS 寡糖衍生探针的微阵列的过程中,我们发现最近购买的一批猪肠黏膜 HS 中 GlcN 残基含量异常高。肝素 lyase III 消化多糖后获得的寡糖的质谱组成和序列分析表明,四糖和六糖部分分别含有两个和三个 GlcN。(1)未修饰多糖的 H NMR 表明,与从牛肾和猪肠获得的其他 HS 制剂相比,这种不寻常的批次差异非常明显。通过二糖组成分析确定的 GlcN 含量非常高(30%)和 GlcNAc 含量低(4.2%)表明可能发生了 N-脱乙酰化和/或 N-脱硫酸化。HS 被科学界广泛用于研究 HS 结构和活性。在没有进一步分析的情况下,使用商业 HS 进行 HS 结构特征和 HS 与蛋白质相互作用特异性的研究时,必须谨慎得出结论。在可获得经过验证的商业 HS 参考制剂之前,我们的数据可能对在研究中使用过该制剂的科学界成员有用。