Kumar Kondapi Venkata Pavan, Soueidan Olivier-Mohamad, Cheeseman Christopher I, West Frederick G
Department of Chemistry, University of Alberta, 11227 Saskatchewan Dr., Edmonton, AB, CA, T6G 2G2, Canada.
Department of Physiology, University of Alberta, Medical Sciences Building, Edmonton, AB, CA, T6G 2H7, Canada.
Chemistry. 2017 Jun 12;23(33):8073-8081. doi: 10.1002/chem.201701329. Epub 2017 May 19.
The importance of the hydrogen bonding interactions in the GLUT-hexose binding process (GLUT=hexose transporter) has been demonstrated by studying the binding of structurally modified d-fructose analogues to GLUTs, and in one case its transport into cells. The presence of a hydrogen bond donor at the C-3 position of 2,5-anhydro-d-mannitol derivatives is essential for effective binding to GLUT5 and transport into tumor cells. Surprisingly, installation of a group that can function only as a hydrogen bond acceptor at C-3 resulted in selective recognition by GLUT1 rather than GLUT5. A fluorescently labelled analogue clearly showed GLUT-mediated transport and low efflux properties of the probe. This study reveals that a single positional modification of a 2,5-anhydro-d-mannitol derivative is sufficient to switch its binding preference from GLUT5 to GLUT1, and uncovers general scaffolds that are suitable for the potential selective delivery of molecular payloads into tumor cells via GLUT transport machinery.
通过研究结构修饰的d-果糖类似物与己糖转运蛋白（GLUT）的结合，以及在一个实例中其向细胞内的转运，已证明氢键相互作用在GLUT-己糖结合过程中的重要性。2,5-脱水-d-甘露糖醇衍生物C-3位存在氢键供体对于有效结合GLUT5并转运至肿瘤细胞至关重要。令人惊讶的是，在C-3位安装一个仅能作为氢键受体的基团导致其被GLUT1而非GLUT5选择性识别。一种荧光标记类似物清楚地显示了该探针的GLUT介导的转运和低外排特性。这项研究表明，2,5-脱水-d-甘露糖醇衍生物的单个位置修饰足以将其结合偏好从GLUT5切换至GLUT1，并揭示了适用于通过GLUT转运机制将分子载荷潜在选择性递送至肿瘤细胞的通用支架。
