Primary sequence of cyclic nucleotide phosphodiesterase isozymes and the design of selective inhibitors.
Primary sequence information has been reported for more than 15 different mammalian cyclic nucleotide phosphodiesterases. Moreover, recent observations suggest that many of these isozymes are selectively expressed in a limited number of cell types. The fact that nearly all these different phosphodiesterases have unique primary sequences in their catalytic or regulatory domains and that they are often selectively expressed implies that it may be possible to modulate individual isozymes using specific drugs. Joe Beavo and David Reifsnyder summarize much of the evidence that has led to our current understanding of multiple isozymes of phosphodiesterase, with emphasis on aspects that may be relevant to drug design. They also discuss why many previous attempts to isolate isozyme-selective inhibitors may have failed.
Beavo
J A
JA
Department of Pharmacology, University of Washington, Seattle 98195.
Reifsnyder
D H
DH
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000032:analysis* / Q000037:antagonists & inhibitors; D000818:Animals; D015195:Drug Design; D006801:Humans; D007527:Isoenzymes; D010726:Phosphodiesterase Inhibitors
D007527:Isoenzymes; D010726:Phosphodiesterase Inhibitors; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases