RT info:eu-repo/semantics/article
T1 Small molecule anionophores promote transmembrane anion permeation matching CFTR activity
A1 Hernando Santa Cruz, Elsa
A1 Capurro, Valeria
A1 Cossu, Claudia
A1 Fiore, Michele
A1 García Valverde, María
A1 Soto Cerrato, Vanessa
A1 Pérez Tomás, Ricardo
A1 Moran, Óscar
A1 Zegarra Moran, Olga
A1 Quesada Pato, Roberto
K1 Química orgánica
K1 Chemistry, Organic
AB Anion selective ionophores, anionophores, are small molecules capable of facilitating thetransmembrane transport of anions. Inspired in the structure of natural product prodigiosin, fournovel anionophores 1a-d, including a 1,2,3-triazole group, were prepared. These compounds provedhighly efficient anion exchangers in model phospholipid liposomes. The changes in the hydrogen bondcleft modified the anion transport selectivity exhibited by these compounds compared to prodigiosinand suppressed the characteristic high toxicity of the natural product. Their activity as anionophoresin living cells was studied and chloride efflux and iodine influx from living cells mediated by thesederivatives was demonstrated. These compounds were shown to permeabilize cellular membranesto halides with efficiencies close to the natural anion channel CFTR at doses that do not compromisecellular viability. Remarkably, optimal transport efficiency was measured in the presence of pHgradients mimicking those found in the airway epithelia of Cystic Fibrosis patients. These resultssupport the viability of developing small molecule anionophores as anion channel protein surrogateswith potential applications in the treatment of conditions such as Cystic Fibrosis derived from themalfunction of natural anion transport mechanisms.
PB Nature Research
SN 2045-2322
YR 2018
FD 2018-02
LK http://hdl.handle.net/10259/4873
UL http://hdl.handle.net/10259/4873
LA eng
NO 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)
DS Repositorio Institucional de la Universidad de Burgos
RD 27-dic-2024