2024-03-29T14:25:32Zhttps://riubu.ubu.es/oai/requestoai:riubu.ubu.es:10259/48732024-01-13T19:49:40Zcom_10259_3924com_10259_5086com_10259_2604col_10259_3925
Small molecule anionophores promote transmembrane anion permeation matching CFTR activity
Hernando Santa Cruz, Elsa
Capurro, Valeria
Cossu, Claudia
Fiore, Michele
García Valverde, María
Soto Cerrato, Vanessa
Pérez Tomás, Ricardo
Moran, Óscar
Zegarra Moran, Olga
Quesada Pato, Roberto
Química orgánica
Chemistry, Organic
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.
European Union’s Horizon 2020 research and innovation programme under grant agreement No. 667079, La Marató de TV3 Foundation (20132730), Consejería de Educación de la Junta de Castilla y León (Projects BU340U13 and BU092U16)
2018-08-21T08:54:14Z
2018-08-21T08:54:14Z
2018-02
info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
2045-2322
http://hdl.handle.net/10259/4873
10.1038/s41598-018-20708-3
eng
Scientific Reports. 2018, 8, art. 2608
https://doi.org/10.1038/s41598-018-20708-3
info:eu-repo/grantAgreement/EC/H2020/667079
info:eu-repo/grantAgreement/TV3Foundation/20132730
info:eu-repo/grantAgreement/JCyL/BU340U13
info:eu-repo/grantAgreement/JCyL/BU092U16
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
application/pdf
Nature Research
https://riubu.ubu.es/bitstream/10259/4873/7/Hernando-SR_2018.pdf.jpg
Hispana
TEXT
http://creativecommons.org/licenses/by/4.0/
RIUBU. Repositorio Institucional de la Universidad de Burgos
http://hdl.handle.net/10259/4873