dc.contributor.author
Díaz, Ó.
dc.contributor.author
Martín, V.
dc.contributor.author
Renault, P.
dc.contributor.author
Romero, D.
dc.contributor.author
Guillamon, A.
dc.contributor.author
Giraldo, J.
dc.date.accessioned
2024-03-04T08:38:59Z
dc.date.accessioned
2024-09-19T14:31:10Z
dc.date.available
2024-03-04T08:38:59Z
dc.date.available
2024-09-19T14:31:10Z
dc.date.issued
2023-02-01
dc.identifier.uri
http://hdl.handle.net/2072/537446
dc.description.abstract
Allosteric modulators are of prime interest in drug discovery. These drugs regulate the binding and function of endogenous ligands, with some advantages over orthosteric ligands. A typical pharmacological parameter in allosteric modulation is binding cooperativity. This property can yield unexpected but illuminating results when decomposed into its kinetic parameters. Using two reference models (the allosteric ternary complex receptor model and a heterodimer receptor model), a relationship has been derived for the cooperativity rate constant parameters. This relationship allows many combinations of the cooperativity kinetic parameters for a single binding cooperativity value obtained under equilibrium conditions. This assessment may help understand striking experimental results involving allosteric modulation and suggest further investigations in the field. © 2022 The Authors
und
dc.description.sponsorship
Funding text 1: This project received funding from the European Union’s Horizon2020 research and innovation programme under grant agreement No 848068 and by the grant PID2020-119136RB-I00 funded by MCIN/AEI/10.13039/501100011033. This publication reflects only the authors’ view and the European Commission is not responsible for any use that may be made of the information it contains. A.G. has been funded by grant PID-2021-122954NB-100 funded by MCIN/AEI/10.13039/501100011033 and by ERDF ‘A way of making Europe’. ; Funding text 2: This project received funding from the European Union's Horizon2020 research and innovation programme under grant agreement No 848068 and by the grant PID2020-119136RB-I00 funded by MCIN/AEI/10.13039/501100011033. This publication reflects only the authors’ view and the European Commission is not responsible for any use that may be made of the information it contains. A.G. has been funded by grant PID-2021-122954NB-100 funded by MCIN/AEI/10.13039/501100011033 and by ERDF ‘A way of making Europe’. The authors declare no competing interests.
dc.format.extent
8 p.
cat
dc.publisher
Elsevier Ltd
cat
dc.relation.ispartof
Drug Discovery Today
cat
dc.rights
L'accés als continguts d'aquest document queda condicionat a l'acceptació de les condicions d'ús establertes per la següent llicència Creative Commons: https://creativecommons.org/licenses/by/4.0/
dc.source
RECERCAT (Dipòsit de la Recerca de Catalunya)
dc.subject.other
allosteric modulation; binding cooperativity; binding kinetics; cooperativity rate constant; GPCRs; heterodimer receptor; rate constant; residence time
cat
dc.title
Allosteric binding cooperativity in a kinetic context
cat
dc.type
info:eu-repo/semantics/article
cat
dc.type
info:eu-repo/semantics/publishedVersion
cat
dc.identifier.doi
10.1016/j.drudis.2022.103441
cat
dc.rights.accessLevel
info:eu-repo/semantics/openAccess
