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A Highly Selective Fluorescent Probe for Monitoring the Thyroid Hormone Transporter Activity in Mammalian Cells

Monocarboxylate transporter 8 (MCT8) is a trans‐membrane transporter, which mediates the cellular delivery of thyroid hormones, L‐thyroxine (T4) and 3,5,3′‐triiodo‐L‐thyronine (T3). In humans, the MCT8 protein is encoded by the SLC16A2 gene and mutations in the transporter cause a genetic neurologic...

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Published in:Chemistry : a European journal 2024-09, Vol.30 (54), p.e202401719-n/a
Main Authors: Giri, Debasish, Govindaraj, Vijayakumar, Kumar, Sagar, Ungati, Harinarayana, Mugesh, Govindasamy
Format: Article
Language:English
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Summary:Monocarboxylate transporter 8 (MCT8) is a trans‐membrane transporter, which mediates the cellular delivery of thyroid hormones, L‐thyroxine (T4) and 3,5,3′‐triiodo‐L‐thyronine (T3). In humans, the MCT8 protein is encoded by the SLC16A2 gene and mutations in the transporter cause a genetic neurological disorder known as Allan‐Herndon‐Dudley Syndrome (AHDS). MCT8 deficiency leads to impaired transport of thyroid hormones in the brain. Radiolabelled T4 and T3 or LC/MS‐MS methods have been used to monitor the thyroid hormone uptake through MCT8. Herein, we developed a fluorescent based assay to monitor the thyroid hormone uptake through MCT8. A dansyl‐based fluorescent probe having L‐thyroxine moiety is found to be highly selective towards MCT8 in living cells. The high selectivity of the probe towards MCT8 can be attributed to the halogen bond‐mediated recognition by the transporter protein. The presence of a free carboxylic acid group is essential for the specificity of the probe towards MCT8. Additionally, the selectivity of the probe for MCT8 is abolished upon esterification of the carboxylic group. Similarly, MCT8 does not recognize the probe when it contains a free amine group. This paper describes the first example of a highly selective fluorescent probe for the transmembrane thyroid hormone transporter, monocarboxylate transporter 8 (MCT8). The halogen bond forming ability of the iodine atoms with the transporter and the presence of a free carboxylic acid group are essential for the MCT8 selectivity.
ISSN:0947-6539
1521-3765
1521-3765
DOI:10.1002/chem.202401719