X-ray crystallographic and kinetic investigations of 6-sulfamoyl-saccharin as a carbonic anhydrase inhibitor

2015 ◽  
Vol 13 (13) ◽  
pp. 4064-4069 ◽  
Author(s):  
V. Alterio ◽  
M. Tanc ◽  
J. Ivanova ◽  
R. Zalubovskis ◽  
I. Vozny ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Carbonic Anhydrase Inhibitor ◽  
Carbonic Anhydrase Ii ◽  
X Ray ◽  
Human Carbonic Anhydrase ◽  
Kinetic Investigations

Sulfamoylated saccharin binds to human carbonic anhydrase II through the SO2NH2and not CONHSO2moiety.

scholarly journals The Influence of Varying Fluorination Patterns on the Thermodynamics and Kinetics of Benzenesulfonamide Binding to Human Carbonic Anhydrase II

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 509 ◽  
Author(s):  
Steffen Glöckner ◽  
Khang Ngo ◽  
Björn Wagner ◽  
Andreas Heine ◽  
Gerhard Klebe
Keyword(s):  
Carbonic Anhydrase ◽  
Carbonic Anhydrase Ii ◽  
The Novel ◽  
Binding Modes ◽  
X Ray ◽  
Structure Activity ◽  
Small Set ◽  
Novel Method ◽  
Human Carbonic Anhydrase ◽  
Kinetics Of

The fluorination of lead-like compounds is a common tool in medicinal chemistry to alter molecular properties in various ways and with different goals. We herein present a detailed study of the binding of fluorinated benzenesulfonamides to human Carbonic Anhydrase II by complementing macromolecular X-ray crystallographic observations with thermodynamic and kinetic data collected with the novel method of kinITC. Our findings comprise so far unknown alternative binding modes in the crystalline state for some of the investigated compounds as well as complex thermodynamic and kinetic structure-activity relationships. They suggest that fluorination of the benzenesulfonamide core is especially advantageous in one position with respect to the kinetic signatures of binding and that a higher degree of fluorination does not necessarily provide for a higher affinity or more favorable kinetic binding profiles. Lastly, we propose a relationship between the kinetics of binding and ligand acidity based on a small set of compounds with similar substitution patterns.

scholarly journals Azobenzene-based inhibitors of human carbonic anhydrase II

2015 ◽  
Vol 11 ◽  
pp. 1129-1135 ◽  
Author(s):  
Leander Simon Runtsch ◽  
David Michael Barber ◽  
Peter Mayer ◽  
Michael Groll ◽  
Dirk Trauner ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Catalytic Activity ◽  
Carbonic Anhydrase ◽  
Drug Class ◽  
Carbonic Anhydrase Ii ◽  
Carbonic Anhydrases ◽  
X Ray ◽  
X Ray Crystallography ◽  
Human Carbonic Anhydrase

Aryl sulfonamides are a widely used drug class for the inhibition of carbonic anhydrases. In the context of our program of photochromic pharmacophores we were interested in the exploration of azobenzene-containing sulfonamides to block the catalytic activity of human carbonic anhydrase II (hCAII). Herein, we report the synthesis and in vitro evaluation of a small library of nine photochromic sulfonamides towards hCAII. All molecules are azobenzene-4-sulfonamides, which are substituted by different functional groups in the 4´-position and were characterized by X-ray crystallography. We aimed to investigate the influence of electron-donating or electron-withdrawing substituents on the inhibitory constant K i. With the aid of an hCAII crystal structure bound to one of the synthesized azobenzenes, we found that the electronic structure does not strongly affect inhibition. Taken together, all compounds are strong blockers of hCAII with K i = 25–65 nM that are potentially photochromic and thus combine studies from chemical synthesis, crystallography and enzyme kinetics.

scholarly journals Production and X-ray crystallographic analysis of fully deuterated human carbonic anhydrase II

2005 ◽  
Vol 62 (1) ◽  
pp. 6-9 ◽  
Author(s):  
Monika Budayova-Spano ◽  
S. Zoë Fisher ◽  
Marie-Thérèse Dauvergne ◽  
Mavis Agbandje-McKenna ◽  
David N. Silverman ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Crystallographic Analysis ◽  
Carbonic Anhydrase Ii ◽  
X Ray ◽  
Human Carbonic Anhydrase

Head-to-tail and side-by-side oligomerization of human carbonic anhydrase II: a small angle X-ray scattering study

2001 ◽  
Vol 28 (2) ◽  
pp. 143-150 ◽  
Author(s):  
Marcelo Ceolı́n ◽  
Umbra Sabina Colombo ◽  
Marı́a Cecilia Frate ◽  
Eugenia Clérico ◽  
Erica Antón ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Small Angle ◽  
Carbonic Anhydrase Ii ◽  
X Ray ◽  
X Ray Scattering ◽  
Scattering Study ◽  
Human Carbonic Anhydrase ◽  
Ray Scattering

scholarly journals Preliminary joint neutron and X-ray crystallographic study of human carbonic anhydrase II

2009 ◽  
Vol 65 (5) ◽  
pp. 495-498 ◽  
Author(s):  
S. Z. Fisher ◽  
A. Y. Kovalevsky ◽  
J. F. Domsic ◽  
M. Mustyakimov ◽  
D. N. Silverman ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Carbonic Anhydrase Ii ◽  
X Ray ◽  
Crystallographic Study ◽  
Human Carbonic Anhydrase
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