RESUMEN
We present a cross-species chemogenomic screening platform using libraries of haploid deletion mutants from two yeast species, Saccharomyces cerevisiae and Schizosaccharomyces pombe. We screened a set of compounds of known and unknown mode of action (MoA) and derived quantitative drug scores (or D-scores), identifying mutants that are either sensitive or resistant to particular compounds. We found that compound-functional module relationships are more conserved than individual compound-gene interactions between these two species. Furthermore, we observed that combining data from both species allows for more accurate prediction of MoA. Finally, using this platform, we identified a novel small molecule that acts as a DNA damaging agent and demonstrate that its MoA is conserved in human cells.
Asunto(s)
Antifúngicos/farmacología , Farmacorresistencia Fúngica , Regulación Fúngica de la Expresión Génica/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/genética , Schizosaccharomyces/efectos de los fármacos , Schizosaccharomyces/genética , Antifúngicos/metabolismo , Daño del ADN , Perfilación de la Expresión Génica , Genes Fúngicos , Genoma Fúngico/efectos de los fármacos , Humanos , Mutagénesis , Saccharomyces cerevisiae/metabolismo , Schizosaccharomyces/metabolismo , Eliminación de SecuenciaRESUMEN
Surface enhanced Raman scattering (SERS) has been conducted on tryptophan (W), proline (P) and tyrosine (Y) containing peptides that include W-P-Y, Y-P-W, W-P-P-P-Y, Y-P-P-P-W, W-P-P-P-P-P-Y, and Y-P-P-P-P-P-W to gain insight into molecular binding behavior on a metal substrate to eventually apply in protein SERS detection. The peptides are shown to bind through the molecule's carboxylic end, but the strong affinity of the tryptophan residue to the substrate surface, in conjunction with its large polarizability, dominates each molecule's SERS signal with the strong presence of its ring modes in all samples. These results are important for understanding SERS of protein molecules.