RT info:eu-repo/semantics/article
T1 pH‐dependent chloride transport by pseudopeptidic cages for the selective killing of cancer cells in acidic microenvironments
A1 Tapia, Lucía
A1 Pérez, Yolanda
A1 Bolte, Michael
A1 Casas, Josefina
A1 Solà, Jordi
A1 Quesada Pato, Roberto
A1 Alfonso, Ignacio
K1 Química orgánica
K1 Chemistry, Organic
AB Acidic microenvironments in solid tumors are a hallmark of cancer. Inspired by that, we designed a family of pseudopeptidic cage‐like anionophores displaying pH‐dependent activity. When protonated, they efficiently bind chloride anions. They also transport chloride through lipid bilayers, with their anionophoric properties improving at acidic pH, suggesting an H+/Cl− symport mechanism. NMR studies in DPC micelles demonstrate that the cages bind chloride within the lipid phase. The chloride affinity and the chloride‐exchange rate with the aqueous bulk solution are improved when the pH is lowered. This increases cytotoxicity towards lung adenocarcinoma cells at the pH of the microenvironment of a solid tumor. These properties depend on the nature of the amino‐acid side chains of the cages, which modulate their lipophilicity and interactions with the cell membrane. This paves the way towards using pH as a parameter to control the selectivity of cytotoxic ionophores as anticancer drugs.
PB Wiley
SN 1433-7851
YR 2019
FD 2019-09
LK http://hdl.handle.net/10259/5705
UL http://hdl.handle.net/10259/5705
LA eng
NO MCIU/AEI/FEDER. Grant Number: RTI2018-096182-B-I00 Agència de Gestió d'Ajuts Universitaris i de Recerca. Grant Number: 2017 SGR 208 Junta de Castilla y León. Grant Number: BU092U16 Ministerio de Ciencia e Innovación. Grant Number: BES-2016-076863
DS Repositorio Institucional de la Universidad de Burgos
RD 16-abr-2024