Toward the discovery of new antifungal agents: the design and validation of a novel 2'P-RNA probe and high throughput screening assay against 2'-phosphotransferase Tpt1p.
We report the solid-phase synthesis of novel 2'P-RNA probes for use in fluorescence polarization (FP) ligand binding assays that screens for inhibitors of the yeast 2'- phosphotransferase Tpt1p. The probe was synthesized by utilizing silyl phosphoramidite chemistry and a phosphoramidite synthon containing an orthogonal (DMT) protecting group at its 2'-position. Regioselective removal of the 2'-DMT group and phosphitylation of the unmasked 2'-hydroxyl group afforded the desired 2'P-RNA sequence.
Lackey
Jeremy G
JG
Department of Chemistry, McGill University, Montreal, QC, Canada.
Ron
David
D
Damha
Masad J
MJ
Harding
Heather P
HP
D000935:Antifungal Agents / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005454:Fluorescence Polarization; D005656:Fungal Proteins / Q000037:antagonists & inhibitors*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors*; D015347:RNA Probes / Q000138:chemical synthesis* / Q000737:chemistry; D015003:Yeasts / Q000201:enzymology
D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D015347:RNA Probes; D017853:Phosphotransferases (Alcohol Group Acceptor)