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

Giri, D and Govindaraj, V and Kumar, S and Ungati, H and Mugesh, G (2024) A Highly Selective Fluorescent Probe for Monitoring the Thyroid Hormone Transporter Activity in Mammalian Cells. In: Chemistry - A European Journal, 30 (54).

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Abstract

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. © 2024 Wiley-VCH GmbH.

Item Type:	Journal Article
Publication:	Chemistry - A European Journal
Publisher:	John Wiley and Sons Inc
Additional Information:	The copyright for this article belongs to the publisher.
Keywords:	Animal cell culture; Brain; Carboxylation; Esterification; Genes; Iodine compounds, Cellular delivery; Cellular uptake; Fluorescent molecules; Fluorescent probes; Mammalian cells; Monocarboxylate transporter 8 transporter; Neurological disorders; Thyroid hormones; Thyronine; Transmembranes, Mammals, cotransporter; dansyl chloride; fluorescent dye; liothyronine; monocarboxylate transporter; SLC16A2 protein, human; thyroid hormone; thyroxine, Allan-Herndon-Dudley syndrome; animal; chemistry; HEK293 cell line; human; metabolism; muscle atrophy; muscle hypotonia; transport at the cellular level; X linked mental retardation, Allan-Herndon-Dudley syndrome; Animals; Biological Transport; Dansyl Compounds; Fluorescent Dyes; HEK293 Cells; Humans; Mental Retardation, X-Linked; Monocarboxylic Acid Transporters; Muscle Hypotonia; Muscular Atrophy; Symporters; Thyroid Hormones; Thyroxine; Triiodothyronine
Department/Centre:	Division of Chemical Sciences > Inorganic & Physical Chemistry
Date Deposited:	18 Oct 2024 12:06
Last Modified:	18 Oct 2024 12:06
URI:	http://eprints.iisc.ac.in/id/eprint/86480

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