Arnold Katelyn, Liao Yi-En, Liu Jian
Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
Biomedicines. 2020 Nov 16;8(11):503. doi: 10.3390/biomedicines8110503.
Heparan sulfate is a highly sulfated polysaccharide abundant on the surface of hepatocytes and surrounding extracellular matrix. Emerging evidence demonstrates that heparan sulfate plays an important role in neutralizing the activities of proinflammatory damage associate molecular patterns (DAMPs) that are released from hepatocytes under pathological conditions. Unlike proteins and nucleic acids, isolation of homogenous heparan sulfate polysaccharides from biological sources is not possible, adding difficulty to study the functional role of heparan sulfate. Recent advancement in the development of a chemoenzymatic approach allows production of a large number of structurally defined oligosaccharides. These oligosaccharides are used to probe the physiological functions of heparan sulfate in liver damage under different pathological conditions. The findings provide a potential new therapeutic agent to treat liver diseases that are associated with excessive inflammation.
硫酸乙酰肝素是一种高度硫酸化的多糖,在肝细胞表面和周围的细胞外基质中大量存在。新出现的证据表明,硫酸乙酰肝素在中和病理条件下从肝细胞释放的促炎损伤相关分子模式(DAMPs)的活性方面发挥着重要作用。与蛋白质和核酸不同,从生物来源中分离出同质的硫酸乙酰肝素多糖是不可能的,这增加了研究硫酸乙酰肝素功能作用的难度。化学酶法开发的最新进展使得能够生产大量结构明确的寡糖。这些寡糖被用于探究硫酸乙酰肝素在不同病理条件下肝损伤中的生理功能。这些发现为治疗与过度炎症相关的肝脏疾病提供了一种潜在的新治疗药物。