Cysteine is a building block for several biomolecules that are crucial for living organisms. The last step of cysteine biosynthesis is catalyzed by O-acetylserine sulfydrylase (OASS)., a highly conserved pyridoxal S'-phosphate (PLP)-dependent enzyme, present in different isoforms in bacteria, plants, and nematodes, but absent in mammals. Beside the biosynthesis of cysteine, OASS exerts a series of "moonlighting" activities in bacteria, such as transcriptional regulation, contact-dependent growth inhibition, swarming motility, and induction of antibiotic resistance. Therefore, the discovery of molecules capable of inhibiting OASS would be a valuable tool to unravel how this protein affects the physiology of unicellular organisms. As a continuation of our efforts toward the synthesis of OASS inhibitors, in this work we have used a combination of computational and spectroscopic approaches to rationally design) synthesize, and test a series of substituted 2-phenylcyclopropane carboxylic acids that bind to the two S. typhymurium OASS isoforms at nanomolar concentrations.

Rational Design, Synthesis and Preliminary Structure-Activity Relationships of α-Substituted-2-Phenylcyclopropane Carboxylic Acids as Inhibitors of Salmonella Typhimurium O-Acetylserine Sulfhydrylase / Pieroni, Marco; Annunziato, Giannamaria; Beato, Claudia; Wouters, R.; Benoni, Roberto; Campanini, Barbara; Pertinhez, Thelma; Bettati, Stefano; Mozzarelli, Andrea; Costantino, Gabriele. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 1520-4804. - 59:6(2016), pp. 2567-2578. [10.1021/acs.jmedchem.5b01775]

Rational Design, Synthesis and Preliminary Structure-Activity Relationships of α-Substituted-2-Phenylcyclopropane Carboxylic Acids as Inhibitors of Salmonella Typhimurium O-Acetylserine Sulfhydrylase

PIERONI, Marco;ANNUNZIATO, Giannamaria;BEATO, Claudia;BENONI, Roberto;CAMPANINI, Barbara
;
PERTINHEZ, Thelma;BETTATI, Stefano;MOZZARELLI, Andrea;COSTANTINO, Gabriele
2016-01-01

Abstract

Cysteine is a building block for several biomolecules that are crucial for living organisms. The last step of cysteine biosynthesis is catalyzed by O-acetylserine sulfydrylase (OASS)., a highly conserved pyridoxal S'-phosphate (PLP)-dependent enzyme, present in different isoforms in bacteria, plants, and nematodes, but absent in mammals. Beside the biosynthesis of cysteine, OASS exerts a series of "moonlighting" activities in bacteria, such as transcriptional regulation, contact-dependent growth inhibition, swarming motility, and induction of antibiotic resistance. Therefore, the discovery of molecules capable of inhibiting OASS would be a valuable tool to unravel how this protein affects the physiology of unicellular organisms. As a continuation of our efforts toward the synthesis of OASS inhibitors, in this work we have used a combination of computational and spectroscopic approaches to rationally design) synthesize, and test a series of substituted 2-phenylcyclopropane carboxylic acids that bind to the two S. typhymurium OASS isoforms at nanomolar concentrations.
2016
Rational Design, Synthesis and Preliminary Structure-Activity Relationships of α-Substituted-2-Phenylcyclopropane Carboxylic Acids as Inhibitors of Salmonella Typhimurium O-Acetylserine Sulfhydrylase / Pieroni, Marco; Annunziato, Giannamaria; Beato, Claudia; Wouters, R.; Benoni, Roberto; Campanini, Barbara; Pertinhez, Thelma; Bettati, Stefano; Mozzarelli, Andrea; Costantino, Gabriele. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 1520-4804. - 59:6(2016), pp. 2567-2578. [10.1021/acs.jmedchem.5b01775]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2806191
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 31
  • ???jsp.display-item.citation.isi??? 29
social impact