Small molecule anionophores promote transmembrane anion permeation matching CFTR activity

Abstract Anion selective ionophores, anionophores, are small molecules capable of facilitating the transmembrane transport of anions. Inspired in the structure of natural product prodigiosin, four novel anionophores 1a-d, including a 1,2,3-triazole group, were prepared. These compounds proved highly...

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Autores principales:	Elsa Hernando, Valeria Capurro, Claudia Cossu, Michele Fiore, María García-Valverde, Vanessa Soto-Cerrato, Ricardo Pérez-Tomás, Oscar Moran, Olga Zegarra-Moran, Roberto Quesada
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fc47a172d0f34f89a359a289471393b9
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spelling	oai:doaj.org-article:fc47a172d0f34f89a359a289471393b92021-12-02T15:09:12ZSmall molecule anionophores promote transmembrane anion permeation matching CFTR activity10.1038/s41598-018-20708-32045-2322https://doaj.org/article/fc47a172d0f34f89a359a289471393b92018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-20708-3https://doaj.org/toc/2045-2322Abstract Anion selective ionophores, anionophores, are small molecules capable of facilitating the transmembrane transport of anions. Inspired in the structure of natural product prodigiosin, four novel anionophores 1a-d, including a 1,2,3-triazole group, were prepared. These compounds proved highly efficient anion exchangers in model phospholipid liposomes. The changes in the hydrogen bond cleft modified the anion transport selectivity exhibited by these compounds compared to prodigiosin and suppressed the characteristic high toxicity of the natural product. Their activity as anionophores in living cells was studied and chloride efflux and iodine influx from living cells mediated by these derivatives was demonstrated. These compounds were shown to permeabilize cellular membranes to halides with efficiencies close to the natural anion channel CFTR at doses that do not compromise cellular viability. Remarkably, optimal transport efficiency was measured in the presence of pH gradients mimicking those found in the airway epithelia of Cystic Fibrosis patients. These results support the viability of developing small molecule anionophores as anion channel protein surrogates with potential applications in the treatment of conditions such as Cystic Fibrosis derived from the malfunction of natural anion transport mechanisms.Elsa HernandoValeria CapurroClaudia CossuMichele FioreMaría García-ValverdeVanessa Soto-CerratoRicardo Pérez-TomásOscar MoranOlga Zegarra-MoranRoberto QuesadaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elsa Hernando Valeria Capurro Claudia Cossu Michele Fiore María García-Valverde Vanessa Soto-Cerrato Ricardo Pérez-Tomás Oscar Moran Olga Zegarra-Moran Roberto Quesada Small molecule anionophores promote transmembrane anion permeation matching CFTR activity
description	Abstract Anion selective ionophores, anionophores, are small molecules capable of facilitating the transmembrane transport of anions. Inspired in the structure of natural product prodigiosin, four novel anionophores 1a-d, including a 1,2,3-triazole group, were prepared. These compounds proved highly efficient anion exchangers in model phospholipid liposomes. The changes in the hydrogen bond cleft modified the anion transport selectivity exhibited by these compounds compared to prodigiosin and suppressed the characteristic high toxicity of the natural product. Their activity as anionophores in living cells was studied and chloride efflux and iodine influx from living cells mediated by these derivatives was demonstrated. These compounds were shown to permeabilize cellular membranes to halides with efficiencies close to the natural anion channel CFTR at doses that do not compromise cellular viability. Remarkably, optimal transport efficiency was measured in the presence of pH gradients mimicking those found in the airway epithelia of Cystic Fibrosis patients. These results support the viability of developing small molecule anionophores as anion channel protein surrogates with potential applications in the treatment of conditions such as Cystic Fibrosis derived from the malfunction of natural anion transport mechanisms.
format	article
author	Elsa Hernando Valeria Capurro Claudia Cossu Michele Fiore María García-Valverde Vanessa Soto-Cerrato Ricardo Pérez-Tomás Oscar Moran Olga Zegarra-Moran Roberto Quesada
author_facet	Elsa Hernando Valeria Capurro Claudia Cossu Michele Fiore María García-Valverde Vanessa Soto-Cerrato Ricardo Pérez-Tomás Oscar Moran Olga Zegarra-Moran Roberto Quesada
author_sort	Elsa Hernando
title	Small molecule anionophores promote transmembrane anion permeation matching CFTR activity
title_short	Small molecule anionophores promote transmembrane anion permeation matching CFTR activity
title_full	Small molecule anionophores promote transmembrane anion permeation matching CFTR activity
title_fullStr	Small molecule anionophores promote transmembrane anion permeation matching CFTR activity
title_full_unstemmed	Small molecule anionophores promote transmembrane anion permeation matching CFTR activity
title_sort	small molecule anionophores promote transmembrane anion permeation matching cftr activity
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/fc47a172d0f34f89a359a289471393b9
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Small molecule anionophores promote transmembrane anion permeation matching CFTR activity

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