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- W2005227787 abstract "With this minireview, concepts about how c-AMP and various inhibitor molecules interact with the phosphodiesterases seem to have come full-circle. It will be proposed and elaborated herein that an understanding of SAR for the newest, “second generation” PDE inhibitors is best accomplished by adopting a model that supposes that these compounds are transition state inhibitors. The analysis finds an interesting parallel with early studies where it was recognized that c-AMP adopts a trigonal bipyramid transition state during hydrolysis. The dynamic interaction of ligands with the phosphodiesterase enzymes will also be made evident when simple algebraic expressions are shown to be inadequate for predicting inhibitor potencies. The latter are apparently complicated by cooperative or synergistic relationships that occur among the various binding sites within the receptor. Finally, implications that can be derived from certain topographical features of the model are discussed relative to a range of potential therapeutic indications." @default.
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- W2005227787 date "1991-01-01" @default.
- W2005227787 modified "2023-10-03" @default.
- W2005227787 title "A topographical model for the c-AMP phosphodiesterase III active site" @default.
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- W2005227787 doi "https://doi.org/10.1016/0024-3205(91)90254-9" @default.
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