A fission yeast-based platform for phosphodiesterase inhibitor HTSs and analyses of phosphodiesterase activity.

ABSTRACT: Fission yeast strains have been engineered so that their growth behavior reflects the activity of heterologous cyclic nucleotide phosphodiesterases (PDEs). These strains can be used in High-Throughput Screens (HTSs) for PDE inhibitors that possess "drug-like" characteristics, displaying activity in a growth stimulation assay over a 48-h period. Through three generations of development, a collection of strains expressing 10 of the 11 mammalian PDE families that is appropriate for small molecule inhibitor screening has been generated in our laboratory. Strains unable to synthesize cyclic nucleotides allow characterization of PDE activity in that the enzyme's potency is reflected in the amount of either cAMP or cGMP that must be added to the growth medium to stimulate cell growth. In the futu

SUBMITTER: Demirbas D 

PROVIDER: S-EPMC4417485 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature