Hoffmann Miriam, Snyder Nicole L, Hartmann Laura
Department of Organic Chemistry and Macromolecular Chemistry, Heinrich-Heine-University Düsseldorf, Universitätsstraße 1, 40225 Düsseldorf, Germany.
Department of Chemistry, Davidson College, Davidson, North Carolina 28035, United States.
Macromolecules. 2022 Sep 27;55(18):7957-7973. doi: 10.1021/acs.macromol.2c00675. Epub 2022 Sep 11.
Heparin (HP) and heparan sulfate (HS) are linear, anionically charged polysaccharides well-known for their diverse biological activities. While HP is generally localized in mast cells and in connective tissues, HS is part of the glycocalyx and involved in the attachment of viruses to host cells, constituting the first step of an infection. HP and HS also exhibit antiviral activity by blocking viral receptors, thereby inhibiting viruses from engaging with host cells. Inspired by their structural features, such as their high molecular weight and polyanionic character, various synthetic polymers mimicking HP/HS have been developed and used as model systems to study bioactivity, as well as for therapeutic applications. This Perspective provides an overview of the roles of HP/HS in viral engagement, and examines historical and recent approaches toward oligo-/polysaccharide, glycopolymer, and anionic polymer HP/HS mimetics. An overview of current applications and future prospects of these molecules is provided, demonstrating their potential in addressing current and future epidemics and pandemics.
肝素(HP)和硫酸乙酰肝素(HS)是线性阴离子多糖,以其多样的生物活性而闻名。虽然HP通常定位于肥大细胞和结缔组织中,但HS是糖萼的一部分,并参与病毒与宿主细胞的附着,这是感染的第一步。HP和HS还通过阻断病毒受体表现出抗病毒活性,从而抑制病毒与宿主细胞结合。受其结构特征(如高分子量和聚阴离子特性)的启发,人们开发了各种模拟HP/HS的合成聚合物,并将其用作研究生物活性的模型系统以及用于治疗应用。本观点概述了HP/HS在病毒结合中的作用,并审视了寡糖/多糖、糖聚合物和阴离子聚合物HP/HS模拟物的历史和近期研究方法。还提供了这些分子的当前应用和未来前景的概述,展示了它们在应对当前和未来的流行病和大流行方面的潜力。