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Structural determinants of subtype selectivity and functional activity of angiotensin II receptors
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology. Uppsala Univ, Biomed Ctr, Dept Cell & Mol Biol, Box 596, SE-75124 Uppsala, Sweden..
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2016 (English)In: Bioorganic & Medicinal Chemistry Letters, ISSN 0960-894X, E-ISSN 1090-2120, Vol. 26, no 4, p. 1355-1359Article in journal (Refereed) Published
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Abstract [en]

Agonists of the angiotensin II receptor type 2 (AT(2)), a G-protein coupled receptor, promote tissue protective effects in cardiovascular and renal diseases, while antagonists reduce neuropathic pain. We here report detailed molecular models that explain the AT(2) receptor selectivity of our recent series of non-peptide ligands. In addition, minor structural changes of these ligands that provoke different functional activity are rationalized at a molecular level, and related to the selectivity for the different receptor conformations. These findings should pave the way to structure based drug discovery of AT(2) receptor ligands.

Place, publisher, year, edition, pages
2016. Vol. 26, no 4, p. 1355-1359
Keywords [en]
Angiotensin receptors, Conformational selection, Molecular docking, Homology modeling, Ligand interaction
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-279553DOI: 10.1016/j.bmcl.2015.10.084ISI: 000369377700052PubMedID: 26810314OAI: oai:DiVA.org:uu-279553DiVA, id: diva2:908474
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Swedish Research CouncileSSENCE - An eScience CollaborationAvailable from: 2016-03-02 Created: 2016-03-02 Last updated: 2018-01-10Bibliographically approved

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Sallander, JessicaWallinder, CharlottaHallberg, AndersÅqvist, JohanGutierrez de Teran, Hugo

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Sallander, JessicaWallinder, CharlottaHallberg, AndersÅqvist, JohanGutierrez de Teran, Hugo
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