Department of Chemistry, University of Warwick, Coventry CV4 7AL, U.K.
School of Life Sciences, University of Warwick, Coventry CV4 7AL, U.K.
Biomacromolecules. 2023 Apr 10;24(4):1924-1933. doi: 10.1021/acs.biomac.3c00133. Epub 2023 Mar 28.
Glycopolymers are potent candidates for biomedical applications by exploiting multivalent carbohydrate-lectin interactions. Owing to their specific recognition capabilities, glycosylated polymers can be utilized for targeted drug delivery to certain cell types bearing the corresponding lectin receptors. A fundamental challenge in glycopolymer research, however, is the specificity of recognition to receptors binding to the same sugar unit (e.g., mannose). Variation of polymer backbone chirality has emerged as an effective method to distinguish between lectins on a molecular level. Herein, we present a facile route toward producing glycopolymers with a defined tacticity based on a step-growth polymerization technique using click chemistry. A set of polymers have been fabricated and further functionalized with mannose moieties to enable lectin binding to receptors relevant to the immune system (mannose-binding lectin, dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin, and dendritic and thymic epithelial cell-205). Surface plasmon resonance spectrometry was employed to determine the kinetic parameters of the step-growth glycopolymers. The results highlight the importance of structural complexity in advancing glycopolymer synthesis, yet multivalency remains a main driving force in lectin recognition.
糖聚合物通过利用多价碳水化合物 - 凝集素相互作用，成为生物医学应用的有力候选物。由于其具有特定的识别能力，因此可以将糖基化聚合物用于将药物靶向递送到具有相应凝集素受体的特定细胞类型。然而，糖聚合物研究中的一个基本挑战是与结合相同糖单元（例如甘露糖）的受体的识别特异性。聚合物主链手性的变化已成为在分子水平上区分凝集素的有效方法。在此，我们提出了一种基于点击化学的逐步增长聚合技术来生产具有确定立构规整性的糖聚合物的简便方法。已经制造了一组聚合物，并进一步用甘露糖部分进行功能化，以使凝集素与与免疫系统相关的受体（甘露糖结合凝集素、树突状细胞特异性细胞间黏附分子 3 抓取非整合素和树突状和胸腺上皮细胞 205）结合。表面等离子体共振光谱法用于确定逐步增长糖聚合物的动力学参数。结果强调了结构复杂性在推进糖聚合物合成中的重要性，但多价性仍然是凝集素识别的主要驱动力。
