Biology Reference
In-Depth Information
S. pombe
expression vectors, for either PDE-activating or inhibiting proteins.
Stably incorporating genes expressing such proteins into PDE-expressing strains
would facilitate genetic studies of PDE regulator activity or small molecule screens
similar to those described above. In summary, the introduction of PDEs (which
could include those from nonmammalian sources) into
S. pombe
strains allows for a
wide variety of classical and chemical genetic screens to enhance our understanding
of these enzymes, and to advance the discovery of chemical tools and the develop-
ment of therapeutic compounds.
9 Conclusions
Three generations of strain development has produced a
S. pombe
-based screening
platform that can be used to detect inhibitors of a wide range of full-length PDEs
expressed in a eukaryotic cell. The compounds detected in this manner are stable,
cell permeable, and of low toxicity to
S pombe
, characteristics that may make them
attractive candidates for drug development. In addition to facilitating new inhibitor
discovery and drug development, this system can be used to characterize PDEs and
to study PDEs together with biological regulators in a heterologous system that is
amenable to detecting subtle changes in PDE activity.
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