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J Med Chem. 2013 Nov 14;56(21):8948-8952. doi: 10.1021/jm400539d. Epub 2013 Oct 24.

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

Author information

1
Institut für Organische Chemie, Universität Leipzig, Leipzig, Germany.
2
Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio, USA.
3
Department of Pharmacy, Laboratory of Molecular Pharmacology, University of Patras, Greece.
4
"G.P.Livanos-M.Simou" Laboratories, 1st Department of Critical Care Medicine and Pulmonary Services, Evangelismos Hospital, University of Athens School of Medicine, Athens, Greece.
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Contributed equally

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.

PMID:
24090476
PMCID:
PMC3902542
DOI:
10.1021/jm400539d
[Indexed for MEDLINE]
Free PMC Article

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