2024-03-28T22:59:19Zhttps://riubu.ubu.es/oai/requestoai:riubu.ubu.es:10259/48732024-01-13T19:49:40Zcom_10259_3924com_10259_5086com_10259_2604col_10259_3925
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
2018-02
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.
application/pdf
http://hdl.handle.net/10259/4873
eng
Nature Research
Small molecule anionophores promote transmembrane anion permeation matching CFTR activity
info:eu-repo/semantics/article
TEXT
RIUBU. Repositorio Institucional de la Universidad de Burgos
Hispana