2024-03-29T07:16:31Zhttps://riubu.ubu.es/oai/requestoai:riubu.ubu.es:10259/57052021-11-02T12:01:27Zcom_10259_3924com_10259_5086com_10259_2604col_10259_3925
Tapia, Lucía
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500
Pérez, Yolanda
ad4c62f5-252c-444e-8680-16d10aa21308
500
Bolte, Michael
ce4f3a32-93f0-463d-bed3-b63109a37a12
500
Casas, Josefina
769737a9-f844-42d1-9572-c424b7f2b20a
500
Solà, Jordi
a9ce56cc-0392-4b7f-8612-46d7197559d0
500
Quesada Pato, Roberto
458
500
Alfonso, Ignacio
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500
2021-04-13T11:48:29Z
2021-04-13T11:48:29Z
2019-09
1433-7851
http://hdl.handle.net/10259/5705
10.1002/anie.201905965
1521-3773
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.
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
application/pdf
eng
Wiley
Angewandte Chemie International Edition. 2019, V. 2, n. 36, p. 12465-12468
https://doi.org/10.1002/anie.201905965
info:eu-repo/grantAgreement/AEI/RTI2018-096182-B-I00
info:eu-repo/grantAgreement/JCyL/BU092U16
info:eu-repo/grantAgreement/MICINN/BES-2016-076863
Química orgánica
Chemistry, Organic
pH‐dependent chloride transport by pseudopeptidic cages for the selective killing of cancer cells in acidic microenvironments
info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
info:eu-repo/semantics/openAccess
Angewandte Chemie International Edition
58
36
12465
12468
ORIGINAL
Tapia-acie_2019.pdf
Tapia-acie_2019.pdf
application/pdf
8276720
https://riubu.ubu.es/bitstream/10259/5705/1/Tapia-acie_2019.pdf
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MD5
1
LICENSE
license.txt
license.txt
text/plain; charset=utf-8
999
https://riubu.ubu.es/bitstream/10259/5705/2/license.txt
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MD5
2
THUMBNAIL
Tapia-acie_2019.pdf.jpg
Tapia-acie_2019.pdf.jpg
IM Thumbnail
image/jpeg
4727
https://riubu.ubu.es/bitstream/10259/5705/3/Tapia-acie_2019.pdf.jpg
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MD5
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10259/5705
oai:riubu.ubu.es:10259/5705
2021-11-02 13:01:27.8
Repositorio Institucional de la Universidad de Burgos
bubrep@ubu.es
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