Insights into soluble guanylyl cyclase activation derived from improved heme-mimetics

Margarete Von Wantoch Rekowski; Vijay Kumar; Zongmin Zhou; Johann Moschner; Antonia Marazioti; Marina Bantzi; Georgios A. Spyroulias; Focco Van Den Akker; Athanassios Giannis; Andreas Papapetropoulos

doi:10.1021/jm400539d

Insights into soluble guanylyl cyclase activation derived from improved heme-mimetics

Margarete Von Wantoch Rekowski
, Vijay Kumar
, Zongmin Zhou
, Johann Moschner
, Antonia Marazioti
, Marina Bantzi
, Georgios A. Spyroulias
, Focco Van Den Akker
, Athanassios Giannis
, Andreas Papapetropoulos

Surgery

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	8948-8952
Number of pages	5
Journal	Journal of medicinal chemistry
Volume	56
Issue number	21
DOIs	https://doi.org/10.1021/jm400539d
State	Published - Nov 14 2013

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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10.1021/jm400539d

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abstract = "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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doi = "10.1021/jm400539d",

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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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JO - Journal of medicinal chemistry

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Insights into soluble guanylyl cyclase activation derived from improved heme-mimetics

Abstract

ASJC Scopus subject areas

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