Stefano Elli, Tommaso Sisto, Sofia Nizzolo, Nadia Freato, Laura Bertocchi, Giulio Bianchini, Edwin A Yates, Marco Guerrini
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引用次数: 0
摘要
透明质酸(HA)是一种天然的生物相容性多糖,能与 CD44 受体相互作用,调节炎症、纤维化和组织重建。它是一种适用于给药的化学支架,可以用药理和/或可载体基团进行功能化。通过羧基与 1-氨基-1-脱氧-乳糖醇反应形成酰胺连接,产生接枝聚合物 HYLACH,从而在不同程度上实现 HA 的衍生化。这种聚合物保留了 HA 的广泛特性,尽管与大多数 HA 接枝聚合物一样,这种取代对药物输送系统的设计或优化至关重要,但其详细的构象影响仍然未知。在此,我们利用多种独立的分子动力学模拟对乳糖基化 HA 衍生物的构象、大小、二级结构、氢键网络和水合特性进行了评估。这揭示了 HA 支架微妙但显著的变化,确定了接枝密度是决定其特性的关键参数。
Modeling the Detailed Conformational Effects of the Lactosylation of Hyaluronic Acid.
Hyaluronic acid (HA) is a natural and biocompatible polysaccharide that is able to interact with CD44 receptors to regulate inflammation, fibrosis, and tissue reconstruction. It is a suitable chemical scaffold for drug delivery that can be functionalized with pharmacophores and/or vectorizable groups. The derivatization of HA is achieved to varying extents by reacting 1-amino-1-deoxy-lactitol via the carboxyl group to form amide linkages, giving rise to the grafted polymer, HYLACH. This retains the broad properties of HA, even though, as in most HA-grafted polymers, the detailed conformational effects of such substitutions, while crucial in the design or optimization of drug delivery systems, remain unknown. Here, the conformation, size, secondary structure, hydrogen bond network, and hydration features of lactosylated HA derivatives were evaluated by using multiple independent molecular dynamics simulations. This revealed subtle but nevertheless significant changes in the HA scaffold, establishing the density of grafting as the key parameter determining its properties.
期刊介绍:
Biomacromolecules is a leading forum for the dissemination of cutting-edge research at the interface of polymer science and biology. Submissions to Biomacromolecules should contain strong elements of innovation in terms of macromolecular design, synthesis and characterization, or in the application of polymer materials to biology and medicine.
Topics covered by Biomacromolecules include, but are not exclusively limited to: sustainable polymers, polymers based on natural and renewable resources, degradable polymers, polymer conjugates, polymeric drugs, polymers in biocatalysis, biomacromolecular assembly, biomimetic polymers, polymer-biomineral hybrids, biomimetic-polymer processing, polymer recycling, bioactive polymer surfaces, original polymer design for biomedical applications such as immunotherapy, drug delivery, gene delivery, antimicrobial applications, diagnostic imaging and biosensing, polymers in tissue engineering and regenerative medicine, polymeric scaffolds and hydrogels for cell culture and delivery.