Selective and Tunable Galectin Binding of Glycopolymers Synthesized by a Generalizable Conjugation Method.

Selective and Tunable Galectin Binding of Glycopolymers Synthesized by a Generalizable Conjugation Method.
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DOI:
10.1021/acs.biomac.9b00759
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发表时间:
2019-10-14
期刊:
影响因子:
6.2
通讯作者:
Putnam DA
Putnam DA
中科院分区:
化学2区
文献类型:
--
作者:
Zhou C;Reesink HL;Putnam DA

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糖聚合物是合成聚合物与侧链碳水化合物的缀合物,对于探索碳水化合物在细胞过程中的作用以及生物传感器和药物输送等应用变得越来越重要。通过 DMTMM 偶联将氨基官能化糖接枝到聚丙烯酸上,合成了带有不同糖部分的糖聚合物库。使用氨基甲酸铵在异头(C-1)位置将伯胺引入到许多未受保护的单糖、二糖和三糖中,并与不同分子量的聚(丙烯酸)缀合,通过可逆加成-断裂链转移(RAFT)聚合合成。该方法为制备糖聚合物提供了一种简单有效的途径,其区别仅在于聚合物上糖部分的特性或取代程度。使用表面等离子体共振对这些新型糖聚合物与半乳糖凝集素-1和-3的结合参数(ka、kd和KD)进行定量。半乳糖凝集素选择性地仅与含乳糖聚合物结合,并且结合亲和力取决于半乳糖凝集素类型、糖取代程度和聚合物链的分子量。与半乳糖凝集素-1 和-3 的结合随着糖取代程度的提高和聚合物主链的分子量的增加而增加,达到 10−11 M 左右的 KD 值。
Glycopolymers, conjugates of synthetic polymers with pendant carbohydrates, are becoming increasingly important to probe the role of carbohydrates in cellular processes and for applications like biosensors and drug delivery. A library of glycopolymers bearing different sugar moieties was synthesized by grafting amino-functionalized sugars to poly(acrylic acid) via DMTMM coupling. Primary amines were introduced at the anomeric (C-1) position to a number of unprotected mono-, di-, and trisaccharides using ammonium carbamate and conjugated to poly(acrylic acid) of different molecular weights, synthesized by reversible addition−fragmentation chain transfer (RAFT) polymerization. This approach provides a simple and efficient route for the preparation of glycopolymers that differ only in the identity or degree of substitution of the sugar moiety on the polymer. The binding parameters (ka, kd, and KD) of these new glycopolymers to galectins-1 and −3 were quantified using surface plasmon resonance. The galectins selectively bound only to lactose-containing polymers, and the binding affinity was dependent on the galectin type, degree of sugar substitution and the molecular weight of polymer chains. Binding to both galectin-1 and −3 increased with a higher degree of sugar substitution, and higher molecular weight of the polymer backbone, reaching KD values on the order of 10−11 M.
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影响因子: --
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