Small molecule anionophores promote transmembrane anion permeation matching CFTR activity

Elsa Hernando, Valeria Capurro, Claudia Cossu, Michele Fiore, María García-Valverde, Vanessa Soto-Cerrato, Ricardo Pérez-Tomás, Oscar Moran, Olga Zegarra-Moran, Roberto Quesada

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Article number2608
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

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Permeation
Anions
Molecules
Prodigiosin
Biological Products
Cells
Triazoles
Ionophores
Liposomes
Iodine
Toxicity
Chlorides
Phospholipids
Hydrogen bonds
Derivatives
Membranes
Proteins

ASJC Scopus subject areas

  • General

Cite this

Hernando, E., Capurro, V., Cossu, C., Fiore, M., García-Valverde, M., Soto-Cerrato, V., ... Quesada, R. (2018). Small molecule anionophores promote transmembrane anion permeation matching CFTR activity. Scientific Reports, 8(1), [2608]. https://doi.org/10.1038/s41598-018-20708-3

Small molecule anionophores promote transmembrane anion permeation matching CFTR activity. / Hernando, Elsa; Capurro, Valeria; Cossu, Claudia; Fiore, Michele; García-Valverde, María; Soto-Cerrato, Vanessa; Pérez-Tomás, Ricardo; Moran, Oscar; Zegarra-Moran, Olga; Quesada, Roberto.

In: Scientific Reports, Vol. 8, No. 1, 2608, 01.12.2018.

Research output: Contribution to journalArticle

Hernando, E, Capurro, V, Cossu, C, Fiore, M, García-Valverde, M, Soto-Cerrato, V, Pérez-Tomás, R, Moran, O, Zegarra-Moran, O & Quesada, R 2018, 'Small molecule anionophores promote transmembrane anion permeation matching CFTR activity', Scientific Reports, vol. 8, no. 1, 2608. https://doi.org/10.1038/s41598-018-20708-3
Hernando, Elsa ; Capurro, Valeria ; Cossu, Claudia ; Fiore, Michele ; García-Valverde, María ; Soto-Cerrato, Vanessa ; Pérez-Tomás, Ricardo ; Moran, Oscar ; Zegarra-Moran, Olga ; Quesada, Roberto. / Small molecule anionophores promote transmembrane anion permeation matching CFTR activity. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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