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dc.contributor.authorTapia, Lucía
dc.contributor.authorPérez, Yolanda
dc.contributor.authorBolte, Michael
dc.contributor.authorCasas, Josefina
dc.contributor.authorSolà, Jordi
dc.contributor.authorQuesada Pato, Roberto 
dc.contributor.authorAlfonso, Ignacio
dc.date.accessioned2021-04-13T11:48:29Z
dc.date.available2021-04-13T11:48:29Z
dc.date.issued2019-09
dc.identifier.issn1433-7851
dc.identifier.urihttp://hdl.handle.net/10259/5705
dc.description.abstractAcidic 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.es
dc.description.sponsorshipMCIU/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-2016-076863es
dc.format.mimetypeapplication/pdf
dc.language.isoenges
dc.publisherWileyes
dc.relation.ispartofAngewandte Chemie International Edition. 2019, V. 2, n. 36, p. 12465-12468es
dc.subject.otherQuímica orgánicaes
dc.subject.otherChemistry, Organicen
dc.titlepH‐dependent chloride transport by pseudopeptidic cages for the selective killing of cancer cells in acidic microenvironmentsen
dc.typeinfo:eu-repo/semantics/article
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.relation.publisherversionhttps://doi.org/10.1002/anie.201905965
dc.identifier.doi10.1002/anie.201905965
dc.relation.projectIDinfo:eu-repo/grantAgreement/AEI/RTI2018-096182-B-I00
dc.relation.projectIDinfo:eu-repo/grantAgreement/JCyL/BU092U16
dc.relation.projectIDinfo:eu-repo/grantAgreement/MICINN/BES-2016-076863
dc.identifier.essn1521-3773
dc.journal.titleAngewandte Chemie International Editiones
dc.volume.number58es
dc.issue.number36es
dc.page.initial12465es
dc.page.final12468es
dc.type.hasVersioninfo:eu-repo/semantics/acceptedVersion


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