TY - JOUR
T1 - Insights into soluble guanylyl cyclase activation derived from improved heme-mimetics
AU - Von Wantoch Rekowski, Margarete
AU - Kumar, Vijay
AU - Zhou, Zongmin
AU - Moschner, Johann
AU - Marazioti, Antonia
AU - Bantzi, Marina
AU - Spyroulias, Georgios A.
AU - Van Den Akker, Focco
AU - Giannis, Athanassios
AU - Papapetropoulos, Andreas
PY - 2013/11/14
Y1 - 2013/11/14
N2 - Recently, the structure of BAY 58-2667 bound to the Nostoc sp. H-NOX domain was published. On the basis of this structural information, we designed BAY 58-2667 derivatives and tested their effects on soluble guanylyl cyclase (sGC) activity. Derivative 20 activated sGC 4.8-fold more than BAY 58-2667. Co-crystallization of 20 with the Ns H-NOX domain revealed that the increased conformational distortion at the C-terminal region of αF helix containing 110-114 residues contributes to the higher activation triggered by 20.
AB - Recently, the structure of BAY 58-2667 bound to the Nostoc sp. H-NOX domain was published. On the basis of this structural information, we designed BAY 58-2667 derivatives and tested their effects on soluble guanylyl cyclase (sGC) activity. Derivative 20 activated sGC 4.8-fold more than BAY 58-2667. Co-crystallization of 20 with the Ns H-NOX domain revealed that the increased conformational distortion at the C-terminal region of αF helix containing 110-114 residues contributes to the higher activation triggered by 20.
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U2 - 10.1021/jm400539d
DO - 10.1021/jm400539d
M3 - Article
C2 - 24090476
AN - SCOPUS:84887960499
SN - 0022-2623
VL - 56
SP - 8948
EP - 8952
JO - Journal of medicinal chemistry
JF - Journal of medicinal chemistry
IS - 21
ER -