Friederike Stoll

Publications of Friederike Stoll

• Design and synthesis of the first NO- and haem-independent sGC activator BAY 58–2667 for the treatment of acute decompensated heart failure

  Authors: Michael Hahn, Cristina Alonso-Alija, Friederike Stoll, Markus Heil, Joachim Mittendorf, Karl-Heinz Schlemmer, Frank Wunder, Johannes-Peter Stasch

  BMC Pharmacology. 01/2007;

• Insights into activation and dimerization of soluble guanylate cyclase

  Authors: Christiane Rothkegel, Peter Schmidt, Derek-John Atkins, Friederike Stoll, Henning Schröder, Harald Schmidt, Johannes-Peter Stasch

  BMC Pharmacology. 01/2007;

• Identification of residues crucially involved in soluble guanylate cyclase activation.

  Authors: Christiane Rothkegel, Peter M Schmidt, Friederike Stoll, Henning Schröder, Harald H H W Schmidt, Johannes-Peter Stasch

  FEBS letters. 08/2006; 580(17):4205-13.

  The ubiquitous heterodimeric nitric oxide (NO) receptor soluble guanylate cyclase (sGC) plays a key role in various signal transduction pathways. Binding of NO takes place at the prosthetic hemeThe ubiquitous heterodimeric nitric oxide (NO) receptor soluble guanylate cyclase (sGC) plays a key role in various signal transduction pathways. Binding of NO takes place at the prosthetic heme moiety at the N-terminus of the beta(1)-subunit of sGC. The induced structural changes lead to an activation of the catalytic C-terminal domain of the enzyme and to an increased conversion of GTP into the second messenger cyclic GMP (cGMP). In the present work we selected and substituted different residues of the sGC heme-binding pocket based on a sGC homology model. The generated sGC variants were tested in a cGMP reporter cell for their effect on the enzyme activation by heme-dependent (NO, BAY 41-2272) stimulators and heme-independent (BAY 58-2667) activators. The use of these experimental tools allows the enzyme's heme content to be explored in a non-invasive manner. Asp(44), Asp(45) and Phe(74) of the beta(1)-subunit were identified as being crucially important for functional enzyme activation. beta(1)Asp(45) may serve as a switch between different conformational states of sGC and point to a possible mechanism of action of the heme dependent sGC stimulator BAY 41-2272. Furthermore, our data shows that the activation profile of beta(1)IIe(145) Tyr is unchanged compared to the native enzyme, suggesting that Tyr(145) does not confer the ability to distinguish between NO and O(2). In summary, the present work further elucidated intramolecular mechanisms underlying the NO- and BAY 41-2272-mediated sGC activation and raises questions regarding the postulated role of Tyr(145) for ligand discrimination.

• Beyond NO and heme: biochemical and pharmacological opportunities

  Authors: Christiane Rothkegel, Peter Schmidt, Arun HS, Friederike Stoll, Harald Lapp, Frank Wunder, Henning Schröder, Matthias Rinke, Harald Schmidt, Johannes-Peter Stasch

  BMC Pharmacology. 01/2005;

• Residues stabilizing the heme moiety of the NO sensor soluble guanylate cyclase

  Authors: Peter Schmidt, Christiane Rothkegel, Frank Wunder, Friederike Stoll, Henning Schröder, Johannes-Peter Stasch

  BMC Pharmacology. 01/2005;