Heide Fabian, Koch Manuel, Stetefeld Jörg
Department of Chemistry, University of Manitoba, Winnipeg, MB R3T 2N2, Canada.
Institute for Experimental Dental Research and Oral Musculoskeletal Biology, Center for Biochemistry, Medical Faculty, University of Cologne, 50931 Cologne, Germany.
Pharmaceuticals (Basel). 2023 Mar 22;16(3):471. doi: 10.3390/ph16030471.
Heparan sulfate is a crucial extracellular matrix component that organizes structural features and functional protein processes. This occurs through the formation of protein-heparan sulfate assemblies around cell surfaces, which allow for the deliberate local and temporal control of cellular signaling. As such, heparin-mimicking drugs can directly affect these processes by competing with naturally occurring heparan sulfate and heparin chains that then disturb protein assemblies and decrease regulatory capacities. The high number of heparan-sulfate-binding proteins that are present in the extracellular matrix can cause obscure pathological effects that should be considered and examined in more detail, especially when developing novel mimetics for clinical use. The objective of this article is to investigate recent studies that present heparan-sulfate-mediated protein assemblies and the impact of heparin mimetics on the assembly and function of these protein complexes.
硫酸乙酰肝素是一种关键的细胞外基质成分,它组织构建结构特征并参与功能性蛋白质过程。这一过程通过在细胞表面形成蛋白质 - 硫酸乙酰肝素组装体来实现,从而实现对细胞信号传导进行精确的局部和时间控制。因此,肝素模拟药物可以通过与天然存在的硫酸乙酰肝素和肝素链竞争,直接影响这些过程,进而干扰蛋白质组装并降低调节能力。细胞外基质中存在大量硫酸乙酰肝素结合蛋白,这可能会导致一些模糊不清的病理效应,在开发新型临床用模拟物时,尤其应予以考虑并更详细地研究。本文的目的是探讨近期有关硫酸乙酰肝素介导的蛋白质组装以及肝素模拟物对这些蛋白质复合物组装和功能影响的研究。