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Updated: May 17, 2025

Detection of Detergent-sensitive Interactions Between Membrane Proteins
Published on: March 7, 2018
Identification of Rapaglutin E as an Isoform-Specific Inhibitor of Glucose Transporter 1
Marnie Kotlyar1,2,3, Zufeng Guo2,3, A V Subba Rao2,3
1Chemistry Biology Interface Graduate Program, Johns Hopkins University, Baltimore, Maryland 21218, United States.
Abstract:
Natural products rapamycin and FK506 are macrocyclic compounds with therapeutic benefits whose unique scaffold inspired the generation and exploration of hybrid macrocycle rapafucins. From this library, a potent inhibitor of the facilitative glucose transporter (GLUT), rapaglutin A (RgA), was previously identified. RgA is a pan-GLUT inhibitor of Class I isoforms GLUT1, GLUT3, and GLUT4. Herein, we report the discovery of rapaglutin E (RgE). Unlike RgA, RgE is highly specific for GLUT1. Further characterization revealed that RgE and RgA likely bound to distinct sites on GLUT1 despite their shared FKBP-binding domain, suggesting that the distinct effector domains of RgE and RgA play key roles in the recognition of GLUTs.
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