Introducing affinity and selectivity into galectin-targeting nanoparticles with fluorinated glycan ligands.

Introducing affinity and selectivity into galectin-targeting nanoparticles with fluorinated glycan ligands.
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将亲和力和选择性引入带有氟化聚糖配体的靶向元素靶向纳米颗粒。

DOI:
10.1039/d0sc05360k
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发表时间:
2020-11-16
期刊:
影响因子:
8.4
通讯作者:
Gibson MI
Gibson MI
中科院分区:
化学1区
文献类型:
--
作者:
Richards SJ;Keenan T;Vendeville JB;Wheatley DE;Chidwick H;Budhadev D;Council CE;Webster CS;Ledru H;Baker AN;Walker M;Galan MC;Linclau B;Fascione MA;Gibson MI

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凝集素是潜在的生物标志物和治疗靶点。然而,半乳糖凝集素对β-半乳糖苷具有广泛的亲和力,这意味着基于聚糖的(纳米)生物传感器缺乏所需的选择性和亲和力。利用聚合物稳定的纳米粒子生物传感平台,我们在此证明了固定化乳糖- n -二糖对凝集素的特异性可以通过使用位点特异性聚糖氟化来“打开/关闭”,并且在某些情况下可以实现特异性的逆转。利用婴儿双歧杆菌中的BiGalK和BiGalHexNAcP酶,通过化学酶法获得了含氟聚糖的面板,这两种酶对含氟聚糖具有耐受性,引入了结构多样性,而单独使用化学方法是非常困难的。这些结果表明,将非天然的氟化聚糖整合到纳米材料中可以编码前所未有的选择性,在生物传感方面具有潜在的应用前景。采用化学-酶位点特异性氟化策略获得糖纳米颗粒,可调节对凝集素的选择性。
Galectins are potential biomarkers and therapeutic targets. However, galectins display broad affinity towards β-galactosides meaning glycan-based (nano)biosensors lack the required selectivity and affinity. Using a polymer-stabilized nanoparticle biosensing platform, we herein demonstrate that the specificity of immobilised lacto-N-biose towards galectins can be ‘turned on/off’ by using site-specific glycan fluorination and in some cases reversal of specificity can be achieved. The panel of fluoro-glycans were obtained by a chemoenzymatic approach, exploiting BiGalK and BiGalHexNAcP enzymes from Bifidobacterium infantis which are shown to tolerate fluorinated glycans, introducing structural diversity which would be very laborious by chemical methods alone. These results demonstrate that integrating non-natural, fluorinated glycans into nanomaterials can encode unprecedented selectivity with potential applications in biosensing. A chemo-enzymatic site-specific fluorination strategy is employed to obtain glyco-nanoparticles with tuneable selectivity towards galectins.
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