Laboratory for Biomaterials, Institute for Biotechnology and Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University, Pauwelsstraße 20, D-52074 Aachen, Germany; Equally contributing authors.
Institute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, CZ-14220 Prague 4, Czech Republic; Equally contributing authors.
Trends Biotechnol. 2019 Apr;37(4):402-415. doi: 10.1016/j.tibtech.2018.10.001. Epub 2018 Nov 6.
Cellular communication events are mediated by interactions between cell-surface sugars and lectins, which are carbohydrate-binding proteins. Galectins are β-galactosyl-binding lectins that bridge molecules by their sugar moieties, forming a signaling and adhesion network. Severe changes in glycosylation and galectin expression accompany major processes in oncogenesis, cardiovascular disorders, and other pathologies, making galectins attractive therapeutic targets. Here we discuss advanced strategies of chemo-enzymatic carbohydrate synthesis for creating lead glycomimetics and (neo-)glycoconjugates for galectin-1 and -3 targeting in biomedicine and biotechnology. We will describe the challenges and bottlenecks on the route into biomedical and biotechnological practice and present the first clinical candidates. The coming era will see an exciting translation of selective well-defined high-affinity galectin ligands from bench to bedside.
细胞通讯事件是由细胞表面糖和凝集素（糖结合蛋白）之间的相互作用介导的。半乳糖凝集素是通过其糖部分连接分子的 β-半乳糖基结合凝集素，形成信号和粘附网络。糖基化和半乳糖凝集素表达的严重变化伴随着肿瘤发生、心血管疾病和其他病理学中的主要过程，使半乳糖凝集素成为有吸引力的治疗靶点。在这里，我们讨论了用于创建针对半乳糖凝集素 1 和 3 的先导糖模拟物和（新）糖缀合物的化学酶碳水化合物合成的先进策略，用于生物医学和生物技术。我们将描述进入生物医学和生物技术实践的路线上的挑战和瓶颈，并介绍第一批临床候选物。未来将看到从实验室到临床的具有高选择性和高亲和力的半乳糖凝集素配体的令人兴奋的转化。
