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

Research output: Contribution to journalArticlepeer-review


  • Tom Podewin
  • Johannes Broichhagen
  • Christina Frost
  • Dieter Groneberg
  • Helena Meyer-Berg
  • Nicholas H.F. Fine
  • Andreas Friebe
  • Martin Zacharias
  • Dirk Trauner
  • Anja Hoffmann-Röder

Colleges, School and Institutes

External organisations

  • LMU Munich; Department of Chemistry and Center for Integrated Protein Science (CIPSM); Butenandtstrasse 5-13 81377 Munich Germany
  • Department of Physics, Technical University of Munich, James-Franck-Str. 1, 85748 Garching, Germany
  • Julius-Maximillan-University Wurzburg, Institute of Physiology, Rontgenring 9, 97070 Wurzburg, Germany
  • Department of Chemistry, Ludwig-Maximilians-Universitat Muchen, and Munich Center for Integrated Protein Science, Butenandtstrasse 5-13, 81377 Muchen, Germany


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.


Original languageEnglish
Pages (from-to)4644-4653
JournalChemical Science
Issue number6
Early online date19 Apr 2017
Publication statusPublished - Jun 2017