Department of Chemistry, University of Alberta, Edmonton, AB T6G 2G2, Canada.
Department of Chemistry, Stanford University, Stanford, CA 94305, USA.
Cell Chem Biol. 2024 Nov 21;31(11):1986-2001.e9. doi: 10.1016/j.chembiol.2024.09.010. Epub 2024 Oct 24.
Selective detection of disease-associated changes in the glycocalyx is an emerging field in modern targeted therapies. Detecting minor glycan changes on the cell surface is a challenge exacerbated by the lack of correspondence between cellular DNA/RNA and glycan structures. We demonstrate that multivalent displays of lectins on DNA-barcoded phages-liquid lectin array (LiLA)-detect subtle differences in density of glycans on cells. LiLA constructs displaying 73 copies of diCBM40 (CBM) lectin per virion (φ-CBM) exhibit non-linear ON/OFF-like recognition of sialoglycans on the surface of normal and cancer cells. A high-valency φ-CBM display, or soluble CBM protein, cannot amplify the subtle differences detected by φ-CBM. Similarly, multivalent displays of CBM and Siglec-7 detect differences in the glycocalyx between stem-like and non-stem populations in cancer. Multivalent display of lectins offer in situ detection of minor differences in glycocalyx in cells both in vitro and in vivo not feasible to currently available technologies.
糖萼相关疾病变化的选择性检测是现代靶向治疗中的一个新兴领域。由于细胞 DNA/RNA 和聚糖结构之间缺乏对应关系，因此检测细胞表面上微小的聚糖变化是一项具有挑战性的工作。我们证明，DNA 编码噬菌体上多价展示的凝集素-液体凝集素阵列（LiLA）-可以检测细胞上聚糖密度的细微差异。每个噬菌体展示 73 个二连接的 CBM40（CBM）凝集素的 LiLA 构建体（φ-CBM）表现出对正常和癌细胞表面唾液糖的非线性 ON/OFF 样识别。高价 φ-CBM 显示或可溶性 CBM 蛋白不能放大 φ-CBM 检测到的细微差异。同样，CBM 和 Siglec-7 的多价展示可以检测出癌症中干细胞样和非干细胞样群体之间糖萼的差异。凝集素的多价展示提供了在体外和体内检测细胞中糖萼中微小差异的方法，这是目前现有技术无法实现的。
