Chemical Approaches for Studying the Biology and Pharmacology of Membrane Transporters: The Histidine/Large Amino Acid Transporter SLC7A5 as a Benchmark

The localization of membrane transporters at the forefront of natural barriers makes these proteins very interesting due to their involvement in the absorption and distribution of nutrients and xenobiotics, including drugs. Over the years, structure/function relationship studies have been performed...

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Autores principales:	Mariafrancesca Scalise, Raffaella Scanga, Lara Console, Michele Galluccio, Lorena Pochini, Cesare Indiveri
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	membrane transport protein ligands cancer placenta blood brain barrier SLC (SoLute Carriers) Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/572b9f7b46424ad3b7cd0af342687cad
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spelling	oai:doaj.org-article:572b9f7b46424ad3b7cd0af342687cad2021-11-11T18:32:41ZChemical Approaches for Studying the Biology and Pharmacology of Membrane Transporters: The Histidine/Large Amino Acid Transporter SLC7A5 as a Benchmark10.3390/molecules262165621420-3049https://doaj.org/article/572b9f7b46424ad3b7cd0af342687cad2021-10-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6562https://doaj.org/toc/1420-3049The localization of membrane transporters at the forefront of natural barriers makes these proteins very interesting due to their involvement in the absorption and distribution of nutrients and xenobiotics, including drugs. Over the years, structure/function relationship studies have been performed employing several strategies, including chemical modification of exposed amino acid residues. These approaches are very meaningful when applied to membrane transporters, given that these proteins are characterized by both hydrophobic and hydrophilic domains with a different degree of accessibility to employed chemicals. Besides basic features, the chemical targeting approaches can disclose information useful for pharmacological applications as well. An eminent example of this picture is the histidine/large amino acid transporter SLC7A5, known as LAT1 (Large Amino Acid Transporter 1). This protein is crucial in cell life because it is responsible for mediating the absorption and distribution of essential amino acids in peculiar body districts, such as the blood brain barrier and placenta. Furthermore, LAT1 can recognize a large variety of molecules of pharmacological interest and is also considered a hot target for drugs due to its over-expression in virtually all human cancers. Therefore, it is not surprising that the chemical targeting approach, coupled with bioinformatics, site-directed mutagenesis and transport assays, proved fundamental in describing features of LAT1 such as the substrate binding site, regulatory domains and interactions with drugs that will be discussed in this review. The results on LAT1 can be considered to have general applicability to other transporters linked with human diseases.Mariafrancesca ScaliseRaffaella ScangaLara ConsoleMichele GalluccioLorena PochiniCesare IndiveriMDPI AGarticlemembrane transportprotein ligandscancerplacentablood brain barrierSLC (SoLute Carriers)Organic chemistryQD241-441ENMolecules, Vol 26, Iss 6562, p 6562 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	membrane transport protein ligands cancer placenta blood brain barrier SLC (SoLute Carriers) Organic chemistry QD241-441
spellingShingle	membrane transport protein ligands cancer placenta blood brain barrier SLC (SoLute Carriers) Organic chemistry QD241-441 Mariafrancesca Scalise Raffaella Scanga Lara Console Michele Galluccio Lorena Pochini Cesare Indiveri Chemical Approaches for Studying the Biology and Pharmacology of Membrane Transporters: The Histidine/Large Amino Acid Transporter SLC7A5 as a Benchmark
description	The localization of membrane transporters at the forefront of natural barriers makes these proteins very interesting due to their involvement in the absorption and distribution of nutrients and xenobiotics, including drugs. Over the years, structure/function relationship studies have been performed employing several strategies, including chemical modification of exposed amino acid residues. These approaches are very meaningful when applied to membrane transporters, given that these proteins are characterized by both hydrophobic and hydrophilic domains with a different degree of accessibility to employed chemicals. Besides basic features, the chemical targeting approaches can disclose information useful for pharmacological applications as well. An eminent example of this picture is the histidine/large amino acid transporter SLC7A5, known as LAT1 (Large Amino Acid Transporter 1). This protein is crucial in cell life because it is responsible for mediating the absorption and distribution of essential amino acids in peculiar body districts, such as the blood brain barrier and placenta. Furthermore, LAT1 can recognize a large variety of molecules of pharmacological interest and is also considered a hot target for drugs due to its over-expression in virtually all human cancers. Therefore, it is not surprising that the chemical targeting approach, coupled with bioinformatics, site-directed mutagenesis and transport assays, proved fundamental in describing features of LAT1 such as the substrate binding site, regulatory domains and interactions with drugs that will be discussed in this review. The results on LAT1 can be considered to have general applicability to other transporters linked with human diseases.
format	article
author	Mariafrancesca Scalise Raffaella Scanga Lara Console Michele Galluccio Lorena Pochini Cesare Indiveri
author_facet	Mariafrancesca Scalise Raffaella Scanga Lara Console Michele Galluccio Lorena Pochini Cesare Indiveri
author_sort	Mariafrancesca Scalise
title	Chemical Approaches for Studying the Biology and Pharmacology of Membrane Transporters: The Histidine/Large Amino Acid Transporter SLC7A5 as a Benchmark
title_short	Chemical Approaches for Studying the Biology and Pharmacology of Membrane Transporters: The Histidine/Large Amino Acid Transporter SLC7A5 as a Benchmark
title_full	Chemical Approaches for Studying the Biology and Pharmacology of Membrane Transporters: The Histidine/Large Amino Acid Transporter SLC7A5 as a Benchmark
title_fullStr	Chemical Approaches for Studying the Biology and Pharmacology of Membrane Transporters: The Histidine/Large Amino Acid Transporter SLC7A5 as a Benchmark
title_full_unstemmed	Chemical Approaches for Studying the Biology and Pharmacology of Membrane Transporters: The Histidine/Large Amino Acid Transporter SLC7A5 as a Benchmark
title_sort	chemical approaches for studying the biology and pharmacology of membrane transporters: the histidine/large amino acid transporter slc7a5 as a benchmark
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/572b9f7b46424ad3b7cd0af342687cad
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Chemical Approaches for Studying the Biology and Pharmacology of Membrane Transporters: The Histidine/Large Amino Acid Transporter SLC7A5 as a Benchmark

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