Systematic Evaluation of Macromolecular Carbohydrate-Lectin Recognition Using Precision Glycopolymers.

IF 5.5 2区 化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Biomacromolecules Pub Date : 2024-11-06 DOI:10.1021/acs.biomac.4c01245
Cole A Williams, Daniel J Stone, Soumil Y Joshi, Gokhan Yilmaz, Parisa Farzeen, Sungjin Jeon, Zamira Harris-Ryden, C Remzi Becer, Sanket A Deshmukh, Cassandra E Callmann
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Abstract

The precise modulation of protein-carbohydrate interactions is critical in glycobiology, where multivalent binding governs key cellular processes. As such, synthetic glycopolymers are useful for probing these interactions. Herein, we developed precision glycopolymers (PGPs) with unambiguous local chemical composition and well-defined global structure and systematically evaluated the effect of polymer length, hydrophobicity, and backbone hybridization as well as glycan density and identity on the binding to both mammalian and plant lectins. Our studies identified glycan density as a critical factor, with PGPs below 50% grafting density showing significantly weaker lectin interactions. Coarse-grained molecular dynamics simulations suggest that the observed phenomena may be due to a decrease in carbohydrate-carbohydrate interactions in fully grafted PGPs, leading to improved solvent accessibility. In functional assays, these PGPs reduced the cell viability and migration in 4T1 breast cancer cells. Our findings establish a structure-activity relationship in glycopolymers, providing new strategies for designing synthetic glycomacromolecules for a myriad of applications.

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利用精密聚糖对大分子碳水化合物-肌球蛋白识别进行系统评估。
精确调节蛋白质与碳水化合物的相互作用在糖生物学中至关重要,因为多价结合控制着关键的细胞过程。因此,合成糖聚合物有助于探究这些相互作用。在这里,我们开发了具有明确的局部化学成分和定义明确的整体结构的精密聚糖(PGPs),并系统地评估了聚合物长度、疏水性、骨架杂交以及聚糖密度和特性对哺乳动物和植物凝集素结合的影响。我们的研究发现,聚糖密度是一个关键因素,接枝密度低于 50%的 PGPs 与凝集素的相互作用明显较弱。粗粒度分子动力学模拟表明,观察到的现象可能是由于完全接枝的 PGPs 中碳水化合物与碳水化合物之间的相互作用减弱,从而提高了溶剂的可及性。在功能测试中,这些 PGPs 降低了 4T1 乳腺癌细胞的存活率和迁移率。我们的研究结果建立了糖聚合物的结构-活性关系,为设计合成糖聚合物提供了新的策略,可用于多种应用领域。
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来源期刊
Biomacromolecules
Biomacromolecules 化学-高分子科学
CiteScore
10.60
自引率
4.80%
发文量
417
审稿时长
1.6 months
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.
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