Introducing affinity and selectivity into galectin-targeting nanoparticles with fluorinated glycan ligands,Chemical Science

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Introducing affinity and selectivity into galectin-targeting nanoparticles with fluorinated glycan ligands
Chemical Science ( IF 7.6 ) Pub Date : 2020-11-16 , DOI: 10.1039/d0sc05360k
Sarah-Jane Richards ₁ , Tessa Keenan ₂ , Jean-Baptiste Vendeville ₃ , David E Wheatley ₃ , Harriet Chidwick ₂ , Darshita Budhadev ₂ , Claire E Council ₃ , Claire S Webster ₄ , Helene Ledru ₄ , Alexander N Baker ₁ , Marc Walker ₅ , M Carmen Galan ₄ , Bruno Linclau ₃ , Martin A Fascione ₂ , Matthew I Gibson _{1,

6}

Affiliation

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.

中文翻译：

将亲和力和选择性引入具有氟化聚糖配体的半乳糖素靶向纳米颗粒中

半乳糖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-半乳糖苷表现出广泛的亲和力，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。使用聚合物稳定的纳米颗粒生物传感平台，我们在此证明固定化乳-N-二糖对半乳糖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。这组氟聚糖是通过化学酶法获得的，利用来自婴儿双歧杆菌的 BiGalK 和 BiGalHexNAcP 酶，这些酶显示出耐受氟化聚糖，引入结构多样性，而仅靠化学方法会非常费力。这些结果表明，将非天然氟化聚糖整合到纳米材料中可以编码前所未有的选择性，并在生物传感中具有潜在的应用。

更新日期：2020-11-25

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