In recent years, an approach called “chemical genetics” has been adopted in drug research to discover and validate new targets and to identify and optimize leads by high throughput screening. In this work, we tested the ability of a library of small peptidomimetics to induce phenotypic effects with functional implications on a panel of strains of the budding yeast Saccharomyces cerevisiae, both wild type and mutants, for respiratory function and multidrug resistance. Further elucidation of the function of these peptidomimetics was assessed by testing the effects of the compound with the most prominent inhibitory activity, 089, on gene expression using DNA microarrays. Pathway analysis showed the involvement of such a molecule in inducing oxidative damage through alterations in mitochondrial functions. Transcriptional experiments were confirmed by increased levels of ROS and activation of mitochondrial membrane potential. Our results demonstrate the influence of a functional HAP1 gene in the performance of S. cerevisiae as a model system.

A systems biology approach to dissection of the effects of small bicyclic peptidomimetics on a panel of Saccharomyces cerevisiae mutants / Stefanini, Irene; Trabocchi, Andrea; Marchi, Emmanuela; Guarna, Antonio; Cavalieri, Duccio. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - STAMPA. - 285:(2010), pp. 23477-23485. [10.1074/jbc.M110.125153]

A systems biology approach to dissection of the effects of small bicyclic peptidomimetics on a panel of Saccharomyces cerevisiae mutants

STEFANINI, IRENE;TRABOCCHI, ANDREA;MARCHI, EMMANUELA;GUARNA, ANTONIO;CAVALIERI, DUCCIO
2010

Abstract

In recent years, an approach called “chemical genetics” has been adopted in drug research to discover and validate new targets and to identify and optimize leads by high throughput screening. In this work, we tested the ability of a library of small peptidomimetics to induce phenotypic effects with functional implications on a panel of strains of the budding yeast Saccharomyces cerevisiae, both wild type and mutants, for respiratory function and multidrug resistance. Further elucidation of the function of these peptidomimetics was assessed by testing the effects of the compound with the most prominent inhibitory activity, 089, on gene expression using DNA microarrays. Pathway analysis showed the involvement of such a molecule in inducing oxidative damage through alterations in mitochondrial functions. Transcriptional experiments were confirmed by increased levels of ROS and activation of mitochondrial membrane potential. Our results demonstrate the influence of a functional HAP1 gene in the performance of S. cerevisiae as a model system.
285
23477
23485
Stefanini, Irene; Trabocchi, Andrea; Marchi, Emmanuela; Guarna, Antonio; Cavalieri, Duccio
File in questo prodotto:
File Dimensione Formato  
23477.full.pdf

Accesso chiuso

Tipologia: Versione finale referata (Postprint, Accepted manuscript)
Licenza: DRM non definito
Dimensione 1.73 MB
Formato Adobe PDF
1.73 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in FLORE 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: http://hdl.handle.net/2158/392108
Citazioni
  • ???jsp.display-item.citation.pmc??? 4
  • Scopus 12
  • ???jsp.display-item.citation.isi??? 12
social impact