X-Ray Crystallography and Free Energy Calculations Reveal the Binding Mechanism of A


Journal

Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543

Informations de publication

Date de publication:
14 09 2020
Historique:
received: 13 03 2020
revised: 18 05 2020
pubmed: 17 6 2020
medline: 19 3 2021
entrez: 17 6 2020
Statut: ppublish

Résumé

We present a robust protocol based on iterations of free energy perturbation (FEP) calculations, chemical synthesis, biophysical mapping and X-ray crystallography to reveal the binding mode of an antagonist series to the A

Identifiants

pubmed: 32542862
doi: 10.1002/anie.202003788
pmc: PMC7540567
doi:

Substances chimiques

Purinergic P1 Receptor Antagonists 0
Receptor, Adenosine A2A 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

16536-16543

Informations de copyright

© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

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Auteurs

Willem Jespers (W)

Department of Cell and Molecular Biology, Uppsala University, BMC, Biomedical Center, Box 596, Uppsala, Sweden.

Grégory Verdon (G)

Sosei Heptares, Steinmetz Granta Park, Great Abington, Cambridge, CB21 6DG, UK.

Jhonny Azuaje (J)

Departament of Organic Chemistry, Faculty of Farmacy, Universidade de Santiago de Compostela, Spain.
Centro Singular de Investigación en Química Biolóxica y Materiais Moleculares (CIQUS), Universidade de Santiago de Compostela, Spain.

Maria Majellaro (M)

Departament of Organic Chemistry, Faculty of Farmacy, Universidade de Santiago de Compostela, Spain.
Centro Singular de Investigación en Química Biolóxica y Materiais Moleculares (CIQUS), Universidade de Santiago de Compostela, Spain.

Henrik Keränen (H)

Department of Cell and Molecular Biology, Uppsala University, BMC, Biomedical Center, Box 596, Uppsala, Sweden.
Present address: H. Lundbeck A/S, Ottiliavej 9, 2500, Valby, Denmark.

Xerardo García-Mera (X)

Departament of Organic Chemistry, Faculty of Farmacy, Universidade de Santiago de Compostela, Spain.

Miles Congreve (M)

Sosei Heptares, Steinmetz Granta Park, Great Abington, Cambridge, CB21 6DG, UK.

Francesca Deflorian (F)

Sosei Heptares, Steinmetz Granta Park, Great Abington, Cambridge, CB21 6DG, UK.

Chris de Graaf (C)

Sosei Heptares, Steinmetz Granta Park, Great Abington, Cambridge, CB21 6DG, UK.

Andrei Zhukov (A)

Sosei Heptares, Steinmetz Granta Park, Great Abington, Cambridge, CB21 6DG, UK.

Andrew S Doré (AS)

Sosei Heptares, Steinmetz Granta Park, Great Abington, Cambridge, CB21 6DG, UK.

Jonathan S Mason (JS)

Sosei Heptares, Steinmetz Granta Park, Great Abington, Cambridge, CB21 6DG, UK.

Johan Åqvist (J)

Department of Cell and Molecular Biology, Uppsala University, BMC, Biomedical Center, Box 596, Uppsala, Sweden.

Robert M Cooke (RM)

Sosei Heptares, Steinmetz Granta Park, Great Abington, Cambridge, CB21 6DG, UK.

Eddy Sotelo (E)

Departament of Organic Chemistry, Faculty of Farmacy, Universidade de Santiago de Compostela, Spain.
Centro Singular de Investigación en Química Biolóxica y Materiais Moleculares (CIQUS), Universidade de Santiago de Compostela, Spain.

Hugo Gutiérrez-de-Terán (H)

Department of Cell and Molecular Biology, Uppsala University, BMC, Biomedical Center, Box 596, Uppsala, Sweden.

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Classifications MeSH