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dc.contributorUniversitat Ramon Llull. IQS
dc.contributor.authorCarbajo López, Daniel
dc.contributor.authorGuerra Rebollo, Marta
dc.contributor.authorBujons, Jordi
dc.contributor.authorAlfonso, Ignacio
dc.contributor.authorPrats, Eva
dc.date.accessioned2024-09-06T07:24:27Z
dc.date.available2024-09-06T07:24:27Z
dc.date.issued2022-03-02
dc.identifier.issn0022-2623ca
dc.identifier.urihttp://hdl.handle.net/20.500.14342/4395
dc.description.abstractHeparin-like macromolecules are widely used in clinics as anticoagulant, antiviral, and anticancer drugs. However, the search of heparin antidotes based on small synthetic molecules to control blood coagulation still remains a challenging task due to the physicochemical properties of this anionic polysaccharide. Here, we use a dynamic combinatorial chemistry approach to optimize heparin binders with submicromolar affinity. The recognition of heparin by the most amplified members of the dynamic library has been studied with different experimental (SPR, fluorescence, NMR) and theoretical approaches, rendering a detailed interaction model. The enzymatic assays with selected library members confirm the correlation between the dynamic covalent screening and the in vitro heparin inhibition. Moreover, both ex vivo and in vivo blood coagulation assays with mice show that the optimized molecules are potent antidotes with potential use as heparin reversal drugs. Overall, these results underscore the power of dynamic combinatorial chemistry targeting complex and elusive biopolymers.ca
dc.format.extent13 p.ca
dc.language.isoengca
dc.publisherAmerican Chemical Societyca
dc.relation.ispartofAmerican Chemical Societyca
dc.rights© L'autor/aca
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.otherAssaysca
dc.subject.otherChromatographyca
dc.subject.otherHeparinca
dc.subject.otherLigandsca
dc.subject.otherMoleculesca
dc.subject.otherHeparinaca
dc.subject.otherLligandsca
dc.subject.otherMolèculesca
dc.titleDynamic Combinatorial Optimization of In Vitro and In Vivo Heparin Antidotesca
dc.typeinfo:eu-repo/semantics/articleca
dc.rights.accessLevelinfo:eu-repo/semantics/openAccess
dc.embargo.terms12 mesosca
dc.subject.udc539ca
dc.identifier.doihttps://doi.org/10.1021/acs.jmedchem.1c02054ca
dc.relation.projectIDinfo:eu-repo/grantAgreement/MCI i AEI i FEDER/PN I+D/RTI2018-096182-B-I00ca
dc.relation.projectIDinfo:eu-repo/grantAgreement/MCI i AEI i FEDER/PN I+D/CSIC13-4E-2076ca
dc.relation.projectIDinfo:eu-repo/grantAgreement/SUR del DEC/SGR/2017 SGR 208ca
dc.description.versioninfo:eu-repo/semantics/publishedVersionca


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