RT info:eu-repo/semantics/article
T1 Anion-transport mechanism of a triazole-bearing derivative of prodigiosine: a candidate for cystic fibrosis therapy
A1 Cossu, Claudia
A1 Fiore, Michele
A1 Baroni, Debora
A1 Capurro, Valeria
A1 Caci, Emanuela
A1 García Valverde, María
A1 Quesada Pato, Roberto
A1 Moran, Óscar
K1 cystic fibrosis
K1 ionophore
K1 ion transport
K1 phospholipid vesicles
K1 prodigiosin derivatives
K1 Química orgánica
K1 Chemistry, Organic
AB Cystic fibrosis (CF) is a genetic lethal disease, originated from the defective functionof the CFTR protein, a chloride and bicarbonate permeable transmembrane channel.CF mutations affect CFTR protein through a variety of molecular mechanisms whichresult in different functional defects. Current therapeutic approaches are targeted tospecific groups of patients that share a common functional defect. We seek to developan innovative therapeutic approach for the treatment of CF using anionophores, smallmolecules that facilitate the transmembrane transport of anions. We have characterizedthe anion transport mechanism of a synthetic molecule based on the structure ofprodigiosine, a red pigment produced by bacteria. Anionophore-driven chloride effluxfrom large unilamellar vesicles is consistent with activity of an uniporter carrier thatfacilitates the transport of anions through lipid membranes down the electrochemicalgradient. There are no evidences of transport coupling with protons. The selectivitysequence of the prodigiosin inspired EH160 ionophore is formate > acetate > nitrate> chloride > bicarbonate. Sulfate, phosphate, aspartate, isothionate, and gluconate arenot significantly transported by these anionophores. Protonation at acidic pH is importantfor the transport capacity of the anionophore. This prodigiosin derived ionophore inducesanion transport in living cells. Its low toxicity and capacity to transport chloride andbicarbonate, when applied at low concentration, constitute a promising starting pointfor the development of drug candidates for CF therapy.
PB Frontiers Media
SN 1663-9812
YR 2018
FD 2018-08
LK http://hdl.handle.net/10259/4874
UL http://hdl.handle.net/10259/4874
LA eng
NO European Union’sHorizon 2020 research and innovation programme under grantagreement No 667079 and Consejería de Educación de la Juntade Castilla y León (Project BU092U16).
DS Repositorio Institucional de la Universidad de Burgos
RD 04-dic-2024