RT Journal Article
SR Electronic
T1 Cardiotonic agents. 3. A topographical model of the cardiac cAMP phosphodiesterase receptor.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 1
OP 13
VO 33
IS 1
A1 Erhardt, P W
A1 Hagedorn, A A
A1 Sabio, M
YR 1988
UL http://molpharm.aspetjournals.org/content/33/1/1.abstract
AB Based on the pharmacophoric relationship heterocycle-phenyl-imidazole (H-P-I) and upon consideration of several potent inhibitors of cardiac cAMP phosphodiesterase, a topographical model of this receptor is proposed. The model consists of two binding sites which interact with H, two steric features, preferential rotation of P away from coplanarity with H, and a binding site for an electron-rich system (I). It is supported by molecular modeling studies and accommodates a variety of inhibitors. It also encompasses the active site of the enzyme and can distinguish cAMP from cGMP as substrates.