Inhibition studies of a beta-carbonic anhydrase from Brucella suis with a series of water soluble glycosyl sulfanilamides.

Daniela Vullo (1) , Isao Nishimori (2) , Andrea Scozzafava (1) , Stephan Köhler (3, 4) , Jean-Yves Winum (5) , Claudiu T Supuran (1)

1 LCBI-UniFI - Laboratorio di Chimica Bioinorganica [UniFI, Firenze] = Laboratory of Bioinorganic Chemistry [UniFI Florence]
2 Kochi Medical school
3 IRIM - Institut de Recherche en Infectiologie de Montpellier
4 CPBS - Centre d’études d’Agents Pathogènes et Biotechologies pour la Santé
5 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]

A beta-carbonic anhydrase (CA, EC 4.2.1.1) from the bacterial pathogen Brucella suis, bsCA 1, has been cloned, purified characterized kinetically and for inhibition with a series of water soluble glycosylated sulfanilamides. bsCA 1 has appreciable activity as catalyst for the hydration of CO(2) to bicarbonate, with a k(cat) of 6.4x10(5) s(-1) and k(cat)/K(m) of 3.9x10(7) M(-1) s(-1). All types of inhibitory activities have been detected, with K(I)s in the range of 8.9-110 nM. The best bsCA 1 inhibitor were the galactose and ribose sulfanilamides, with inhibition constants of 8.9-9.2 nM. Small structural changes in the sugar moiety led to dramatic differences of enzyme inhibitory activity for this series of compounds. One of the tested glycosylsulfonamides and acetazolamide significantly inhibited the growth of the bacteria in cell cultures.

Domaines: Bactériologie

Daniela Vullo, Isao Nishimori, Andrea Scozzafava, Stephan Köhler, Jean-Yves Winum, et al.. Inhibition studies of a beta-carbonic anhydrase from Brucella suis with a series of water soluble glycosyl sulfanilamides.. Bioorganic and Medicinal Chemistry Letters, 2010, 20 (7), pp.2178-82. ⟨10.1016/j.bmcl.2010.02.042⟩. ⟨hal-00509066⟩