INNOVENT e. V., Biomaterials Department, Pruessingstrasse 27B, D-07745 Jena, Germany.
Curr Med Chem. 2013;20(20):2501-23. doi: 10.2174/0929867311320200001.
Glycosaminoglycans (GAG) such as hyaluronan (HA) or chondroitin/dermatan sulfate (CS/DS) occur in many connective tissues, for instance, in bone, cartilage and skin. Due to their significant water-binding capacity, GAG are essential for the biomechanical properties of these tissues. However, there is also increasing evidence that the sulfation of GAG does not occur at random, but a "sulfation code" exists that mediates the physiological functions of GAG. Thus, the biological properties of these biomacromolecules are strongly influenced by the degree of sulfation (ds) and the sulfate group distribution along the polymer. Therefore, certain GAG might also have interesting pharmacological properties. It is, thus, commonly accepted that GAG represent promising biomaterials in the field of tissue engineering as well as to design new bioactive materials for tissue repair and reconstruction. In this review we will focus on chemically sulfated GAG and provide a survey of these compounds on four different levels. First, we will provide an overview on chemical functionalization strategies of naturally occurring HA and CS/DS with special emphasis on regioselective methods to introduce a defined number of sulfate residues into the carbohydrate backbone. Second, chemical and biochemical methods to characterize the synthesized compounds will be introduced with the focus on methods based on nuclear magnetic resonance (NMR) and mass spectrometry (MS). In the third part, we will discuss the interaction of natural and chemically sulfated GAG with proteins and other biomolecules with regulatory functions. Additionally, biological consequences of these interactions regarding healing processes of skin and bone will be presented by discussing selected cell culture experiments. Finally, in vivo effects of GAG as components of artificial extracellular matrices will be discussed.
糖胺聚糖（GAG），如透明质酸（HA）或软骨素/硫酸皮肤素（CS/DS），存在于许多结缔组织中，例如骨、软骨和皮肤。由于其具有显著的结合水能力，GAG 是这些组织生物力学特性的基础。然而，越来越多的证据表明，GAG 的硫酸化并非随机发生，而是存在一种“硫酸化密码”，介导 GAG 的生理功能。因此，这些生物大分子的生物学特性受到硫酸化程度（ds）和聚合物上硫酸盐基团分布的强烈影响。因此，某些 GAG 可能也具有有趣的药理学特性。因此，通常认为 GAG 是组织工程领域有前途的生物材料，也是设计用于组织修复和重建的新型生物活性材料的基础。在这篇综述中，我们将重点介绍化学硫酸化 GAG，并从四个不同层面概述这些化合物。首先，我们将提供对天然存在的 HA 和 CS/DS 的化学功能化策略的概述，特别强调引入特定数量硫酸盐残基到糖骨架的区域选择性方法。其次，我们将介绍用于表征合成化合物的化学和生化方法，重点介绍基于核磁共振（NMR）和质谱（MS）的方法。在第三部分，我们将讨论天然和化学硫酸化 GAG 与具有调节功能的蛋白质和其他生物分子的相互作用。此外，还将通过讨论选定的细胞培养实验，介绍这些相互作用在皮肤和骨骼愈合过程中的生物学后果。最后，将讨论作为人工细胞外基质成分的 GAG 的体内作用。
