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  • Cloning, characterization and sulfonamide inhibition studies of an α-carbonic anhydrase from the living fossil sponge Astrosclera willeyana.

Cloning, characterization and sulfonamide inhibition studies of an α-carbonic anhydrase from the living fossil sponge Astrosclera willeyana.

Bioorganic & medicinal chemistry (2012-01-31)
Anna Ohradanova, Daniela Vullo, Silvia Pastorekova, Jaromir Pastorek, Daniel J Jackson, Gert Wörheide, Claudiu T Supuran
ABSTRACT

The α-carbonic anhydrase (CA, EC 4.2.1.1) Astrosclerin-3 previously isolated from the living fossil sponge Astrosclera willeyana (Jackson et al., Science 2007, 316, 1893), was cloned, kinetically characterized and investigated for its inhibition properties with sulfonamides and sulfamates. Astrosclerin-3 has a high catalytic activity for the CO(2) hydration reaction to bicarbonate and protons (k(cat) of 9.0×10(5) s(-1) and k(cat)/K(m) of 1.1×10(8) M(-1) × s(-1)), and is inhibited by various aromatic/heterocyclic sulfonamides and sulfamates with inhibition constants in the range of 2.9 nM-8.85 μM. Astrosclerin, and the human isoform CA II, display similar kinetic properties and affinities for sulfonamide inhibitors, despite more than 550 million years of independent evolution. Because Astrosclerin-3 is involved in biocalcification, the inhibitors characterized here may be used to gain insights into such processes in other metazoans.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Sulfanilamide, ≥98%
Sigma-Aldrich
Sulfamic acid, ACS reagent, 99.3%
Sigma-Aldrich
Saccharin, ≥98%
Supelco
Sulfamic acid, analytical standard (for acidimetry), ACS reagent
Sigma-Aldrich
p-Toluenesulfonamide, ReagentPlus®, ≥99%
Sigma-Aldrich
Sulfanilamide, puriss. p.a., ≥99% (calc. to the dried substance)
Sigma-Aldrich
Sulfamic acid, ReagentPlus®, ≥99%
Sigma-Aldrich
Ammonium sulfamate, ACS reagent, ≥98.0%
Sigma-Aldrich
Saccharin, ≥99%
Sigma-Aldrich
Sulfamic acid, 99.999% trace metals basis
Sigma-Aldrich
Sulfamic acid, reagent grade, 98%
Sigma-Aldrich
Hydrochlorothiazide, crystalline
Sigma-Aldrich
4-Sulfamoylbenzoic acid, 97%
Supelco
Sulfanilamide, VETRANAL®, analytical standard
Sigma-Aldrich
p-Toluenesulfonamide, reagent grade, 98%
Sigma-Aldrich
(±)-Sulpiride
Sigma-Aldrich
Sulfamic acid, ≥99.5% (alkalimetric)
Sigma-Aldrich
Hydrochlorothiazide, meets USP testing specifications
Sigma-Aldrich
Ammonium sulfamate, BioXtra, ≥98.0%