Matović Jelena, Järvinen Juulia, Sokka Iris K, Stockmann Philipp, Kellert Martin, Imlimthan Surachet, Sarparanta Mirkka, Johansson Mikael P, Hey-Hawkins Evamarie, Rautio Jarkko, Ekholm Filip S
Department of Chemistry, University of Helsinki, P.O. Box 55, FI-00014 Helsinki, Finland.
School of Pharmacy, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland.
ACS Omega. 2022 Aug 17;7(34):30376-30388. doi: 10.1021/acsomega.2c03646. eCollection 2022 Aug 30.
Glucose- and sodium-dependent glucose transporters (GLUTs and SGLTs) play vital roles in human biology. Of the 14 GLUTs and 12 SGLTs, the GLUT1 transporter has gained the most widespread recognition because GLUT1 is overexpressed in several cancers and is a clinically valid therapeutic target. We have been pursuing a GLUT1-targeting approach in boron neutron capture therapy (BNCT). Here, we report on surprising findings encountered with a set of 6-deoxy-6-thio-carboranyl d-glucoconjugates. In more detail, we show that even subtle structural changes in the carborane cluster, and the linker, may significantly reduce the delivery capacity of GLUT1-based boron carriers. In addition to providing new insights on the substrate specificity of this important transporter, we reach a fresh perspective on the boundaries within which a GLUT1-targeting approach in BNCT can be further refined.
葡萄糖依赖性和钠依赖性葡萄糖转运蛋白（GLUTs和SGLTs）在人体生物学中发挥着至关重要的作用。在14种GLUTs和12种SGLTs中，GLUT1转运蛋白得到了最广泛的认可，因为GLUT1在多种癌症中过度表达，是一个临床上有效的治疗靶点。我们一直在硼中子俘获疗法（BNCT）中探索靶向GLUT1的方法。在此，我们报告了一组6-脱氧-6-硫代-碳硼烷基-d-葡萄糖共轭物所带来的惊人发现。更详细地说，我们表明，即使碳硼烷簇和连接子中存在细微的结构变化，也可能显著降低基于GLUT1的硼载体的递送能力。除了为这一重要转运蛋白的底物特异性提供新的见解外，我们还对BNCT中靶向GLUT1的方法可以进一步优化的范围有了新的认识。
