The conversion of carbon dioxide (CO2) to bicarbonate (HCO3-) and protons (H+) is a physiologically relevant reaction in all life kingdoms. The uncatalyzed hydration-dehydration reaction CO2 + H2O ⇋ HCO3- + H+ is slow at physiological pH and thus, in biological systems, the reaction is accelerated by enzymatic catalysts, called carbonic anhydrases (CAs, EC 4.2.1.1). CA isozymes have been found in virtually all mammalian tissues and cell types, where they function in CO2 transport and other physiological processes. In the present thesis, it has been carried out a wide study concerning the inhibition profiles of CAs identified in the genome of pathogens causing disease in humans, such as Vibrio cholerae, Plasmodium falciparum, Porphyromonas gingivalis and Malassezia globosa CAs from the pathogens aforementioned were biochemically characterized and an extensive inhibition profile was carried out using the classical CAs inhibitors such as sulfonamides and anions. These studies have contributed to the search of antibiotics with a novel mechanism of action. Additionally, the present thesis has contributed to the discovery of the η-CA, a new genetic families of CAs; to the introduction of a new technique, named protonography, useful for the identification of CA activity on a polyacrylamide gel; and to the phylogenetic analysis of the α-, β- and γ-CAs identified in the genome of the Gram-positive and Gram-negative bacteria.

Inhibition studies of carbonic anhydrases from pathogenic organisms

2017

Abstract

The conversion of carbon dioxide (CO2) to bicarbonate (HCO3-) and protons (H+) is a physiologically relevant reaction in all life kingdoms. The uncatalyzed hydration-dehydration reaction CO2 + H2O ⇋ HCO3- + H+ is slow at physiological pH and thus, in biological systems, the reaction is accelerated by enzymatic catalysts, called carbonic anhydrases (CAs, EC 4.2.1.1). CA isozymes have been found in virtually all mammalian tissues and cell types, where they function in CO2 transport and other physiological processes. In the present thesis, it has been carried out a wide study concerning the inhibition profiles of CAs identified in the genome of pathogens causing disease in humans, such as Vibrio cholerae, Plasmodium falciparum, Porphyromonas gingivalis and Malassezia globosa CAs from the pathogens aforementioned were biochemically characterized and an extensive inhibition profile was carried out using the classical CAs inhibitors such as sulfonamides and anions. These studies have contributed to the search of antibiotics with a novel mechanism of action. Additionally, the present thesis has contributed to the discovery of the η-CA, a new genetic families of CAs; to the introduction of a new technique, named protonography, useful for the identification of CA activity on a polyacrylamide gel; and to the phylogenetic analysis of the α-, β- and γ-CAs identified in the genome of the Gram-positive and Gram-negative bacteria.
2017
Inglese
Claudiu Supuran, Clemente Capasso
Università degli Studi di Firenze
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14242/131768
Il codice NBN di questa tesi è URN:NBN:IT:UNIFI-131768