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Optical control of a receptor-linked guanylyl cyclase using a photoswitchable peptidic hormone

The optical control over biological function with small photoswitchable molecules has gathered significant attention in the last decade. Herein, we describe the design and synthesis of a small library of photoswitchable peptidomimetics based upon human atrial natriuretic peptide (ANP), in which the...

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Autores principales: Podewin, Tom, Broichhagen, Johannes, Frost, Christina, Groneberg, Dieter, Ast, Julia, Meyer-Berg, Helena, Fine, Nicholas H. F., Friebe, Andreas, Zacharias, Martin, Hodson, David J., Trauner, Dirk, Hoffmann-Röder, Anja
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royal Society of Chemistry 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471452/
https://www.ncbi.nlm.nih.gov/pubmed/28626572
http://dx.doi.org/10.1039/c6sc05044a
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author Podewin, Tom
Broichhagen, Johannes
Frost, Christina
Groneberg, Dieter
Ast, Julia
Meyer-Berg, Helena
Fine, Nicholas H. F.
Friebe, Andreas
Zacharias, Martin
Hodson, David J.
Trauner, Dirk
Hoffmann-Röder, Anja
author_facet Podewin, Tom
Broichhagen, Johannes
Frost, Christina
Groneberg, Dieter
Ast, Julia
Meyer-Berg, Helena
Fine, Nicholas H. F.
Friebe, Andreas
Zacharias, Martin
Hodson, David J.
Trauner, Dirk
Hoffmann-Röder, Anja
author_sort Podewin, Tom
collection PubMed
description The optical control over biological function with small photoswitchable molecules has gathered significant attention in the last decade. Herein, we describe the design and synthesis of a small library of photoswitchable peptidomimetics based upon human atrial natriuretic peptide (ANP), in which the photochromic amino acid [3-(3-aminomethyl)phenylazo]phenylacetic acid (AMPP) is incorporated into the peptide backbone. The endogeneous hormone ANP signals via the natriuretic peptide receptor A (NPR-A) through raising intracellular cGMP concentrations, and is involved in blood pressure regulation and sodium homeostasis, as well as lipid metabolism and pancreatic function. The cis- and trans-isomers of one of our peptidomimetics, termed TOP271, exhibit a four-fold difference in NPR-A mediated cGMP synthesis in vitro. Despite this seemingly small difference, TOP271 enables large, optically-induced conformational changes ex vivo and transforms the NPR-A into an endogenous photoswitch. Thus, application of TOP271 allows the reversible generation of cGMP using light and remote control can be afforded over vasoactivity in explanted murine aortic rings, as well as pancreatic beta cell function in islets of Langerhans. This study demonstrates the broad applicability of TOP271 to enzyme-dependent signalling processes, extends the toolbox of photoswitchable molecules to all classes of transmembrane receptors and utilizes photopharmacology to deduce receptor activation on a molecular level.
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spelling pubmed-54714522017-06-16 Optical control of a receptor-linked guanylyl cyclase using a photoswitchable peptidic hormone Podewin, Tom Broichhagen, Johannes Frost, Christina Groneberg, Dieter Ast, Julia Meyer-Berg, Helena Fine, Nicholas H. F. Friebe, Andreas Zacharias, Martin Hodson, David J. Trauner, Dirk Hoffmann-Röder, Anja Chem Sci Chemistry The optical control over biological function with small photoswitchable molecules has gathered significant attention in the last decade. Herein, we describe the design and synthesis of a small library of photoswitchable peptidomimetics based upon human atrial natriuretic peptide (ANP), in which the photochromic amino acid [3-(3-aminomethyl)phenylazo]phenylacetic acid (AMPP) is incorporated into the peptide backbone. The endogeneous hormone ANP signals via the natriuretic peptide receptor A (NPR-A) through raising intracellular cGMP concentrations, and is involved in blood pressure regulation and sodium homeostasis, as well as lipid metabolism and pancreatic function. The cis- and trans-isomers of one of our peptidomimetics, termed TOP271, exhibit a four-fold difference in NPR-A mediated cGMP synthesis in vitro. Despite this seemingly small difference, TOP271 enables large, optically-induced conformational changes ex vivo and transforms the NPR-A into an endogenous photoswitch. Thus, application of TOP271 allows the reversible generation of cGMP using light and remote control can be afforded over vasoactivity in explanted murine aortic rings, as well as pancreatic beta cell function in islets of Langerhans. This study demonstrates the broad applicability of TOP271 to enzyme-dependent signalling processes, extends the toolbox of photoswitchable molecules to all classes of transmembrane receptors and utilizes photopharmacology to deduce receptor activation on a molecular level. Royal Society of Chemistry 2017-06-01 2017-04-19 /pmc/articles/PMC5471452/ /pubmed/28626572 http://dx.doi.org/10.1039/c6sc05044a Text en This journal is © The Royal Society of Chemistry 2017 http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Chemistry
Podewin, Tom
Broichhagen, Johannes
Frost, Christina
Groneberg, Dieter
Ast, Julia
Meyer-Berg, Helena
Fine, Nicholas H. F.
Friebe, Andreas
Zacharias, Martin
Hodson, David J.
Trauner, Dirk
Hoffmann-Röder, Anja
Optical control of a receptor-linked guanylyl cyclase using a photoswitchable peptidic hormone
title Optical control of a receptor-linked guanylyl cyclase using a photoswitchable peptidic hormone
title_full Optical control of a receptor-linked guanylyl cyclase using a photoswitchable peptidic hormone
title_fullStr Optical control of a receptor-linked guanylyl cyclase using a photoswitchable peptidic hormone
title_full_unstemmed Optical control of a receptor-linked guanylyl cyclase using a photoswitchable peptidic hormone
title_short Optical control of a receptor-linked guanylyl cyclase using a photoswitchable peptidic hormone
title_sort optical control of a receptor-linked guanylyl cyclase using a photoswitchable peptidic hormone
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471452/
https://www.ncbi.nlm.nih.gov/pubmed/28626572
http://dx.doi.org/10.1039/c6sc05044a
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