Temperature switchable glycopolymers and their conformation-dependent binding to receptor targets.

Temperature switchable glycopolymers and their conformation-dependent binding to receptor targets.
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温度可切换的糖聚合物及其与受体靶标的构象依赖性结合

DOI:
10.1021/acs.biomac.0c00676
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发表时间:
2020
期刊:
影响因子:
6.2
通讯作者:
Schmidt
Schmidt
中科院分区:
化学2区
文献类型:
--
作者:
Strzelczyk;Feldhof;Schmidt

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研究了由聚n -异丙基丙烯酰胺(PNIPAM)和甘露糖配体组成的共聚物与大肠杆菌和豆豆蛋白A (ConA)的温度依赖性结合。以聚(n -丙烯氧基琥珀酰亚胺)和不同连接剂的氨基连接甘露糖残基为原料,通过聚合物模拟反应制备了甘露糖密度不同的糖共聚物。定量黏附抑制实验表明,甘聚糖共聚物的抑制潜力与甘露糖/NIPAM的比例和连接剂类型有关,在其最低临界溶液温度(LCST)上下。有趣的是,温度对结合脚趾的影响相反。观察到colian和ConA。而你。总的来说,在温度升高时,ConA的抑制作用较弱。当超过LCST时,聚合物经历线圈到球体的转变,形成具有表面富集的亲水糖部分的微相,表现出增加的ede。通过空间屏蔽抑制大肠杆菌。然而,在LCST之上形成的这种微相使得一部分碳水化合物配体无法进入,而留在溶液中的聚合物的线圈大小低于ConA受体的最小结合位点间距,这解释了ConA抑制作用的降低。总的来说,这些结果表明,由于空间屏蔽和碳水化合物配体可及性的不利影响,糖共聚物的线圈到球体的转变可能会引起更低或更高的抑制电位。
The temperature-dependent binding of copolymers from poly(N-isopropylacrylamide) (PNIPAM) and mannose ligands toEscherichia coliand concanavalin A (ConA) is determined. Through polymer analogous reactions using poly(N-acryloxysuccinimide) and amine-linked mannose residues with different linkers, glycopolymers are prepared with the variation of the mannose density. Quantitative adhesion inhibition assays show the inhibitory potential of the glycopolymers as a function of the mannose/NIPAM ratio and linker type above and below their lower critical solution temperature (LCST). Intriguingly, opposite temperature effects on the binding toE. coliand ConA are observed. While theE. coliinhibition is stronger above the LCST, the ConA inhibition is, in overall, weaker at elevated temperatures. When going beyond the LCST, the polymers undergo a coil-to-globule transition, forming microphases with surface-enriched hydrophilic sugar moieties exhibiting increasedE. coliinhibition through steric shielding. However, the formation of such microphases above the LCST renders a fraction of carbohydrate ligands inaccessible,and the polymers remaining in the solution phase then have coil sizes below the minimum binding site spacing of the ConA receptor, explaining reduced ConA inhibition. Overall, these results suggest that the coil-to-globule transition of glycopolymers may induce lower or higher inhibitory potentials due to the adverse effects of steric shielding and carbohydrate ligand accessibility.
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