Arlov Øystein, Skjåk-Bræk Gudmund
Department of Biotechnology and Nanomedicine, SINTEF Materials and Chemistry, Richard Birkelands vei 3B, 7034 Trondheim, Norway.
Department of Biotechnology, Norwegian University of Science and Technology, Sem Sælands vei 6/8, 7034 Trondheim, Norway.
Molecules. 2017 May 11;22(5):778. doi: 10.3390/molecules22050778.
Heparin is widely recognized for its potent anticoagulating effects, but has an additional wide range of biological properties due to its high negative charge and heterogeneous molecular structure. This heterogeneity has been one of the factors in motivating the exploration of functional analogues with a more predictable modification pattern and monosaccharide sequence, that can aid in elucidating structure-function relationships and further be structurally customized to fine-tune physical and biological properties toward novel therapeutic applications and biomaterials. Alginates have been of great interest in biomedicine due to their inherent biocompatibility, gentle gelling conditions, and structural versatility from chemo-enzymatic engineering, but display limited interactions with cells and biomolecules that are characteristic of heparin and the other glycosaminoglycans (GAGs) of the extracellular environment. Here, we review the chemistry and physical and biological properties of sulfated alginates as structural and functional heparin analogues, and discuss how they may be utilized in applications where the use of heparin and other sulfated GAGs is challenging and limited.
肝素因其强大的抗凝作用而被广泛认可,但其高负电荷和异质分子结构使其具有一系列额外的生物学特性。这种异质性一直是促使人们探索具有更可预测修饰模式和单糖序列的功能类似物的因素之一,这些类似物有助于阐明结构-功能关系,并进一步在结构上进行定制,以微调物理和生物学特性,用于新型治疗应用和生物材料。由于其固有的生物相容性、温和的凝胶化条件以及化学酶工程赋予的结构多样性,海藻酸盐在生物医学领域备受关注,但与细胞和生物分子的相互作用有限,而这些相互作用是肝素和细胞外环境中其他糖胺聚糖(GAGs)的特征。在此,我们综述了硫酸化海藻酸盐作为结构和功能肝素类似物的化学、物理和生物学特性,并讨论了在肝素和其他硫酸化GAGs的使用具有挑战性且受限的应用中,它们如何得到利用。