Stable analogs of acyl adenylates. Inhibition of acetyl- and acyl-CoA synthetase by adenosine 5'-alkylphosphates

Abstract

Adenosine 5'-alkylphosphates are potent inhibitors of acetyl- and acyl-CoA synthetase. In each case, the most effective inhibitor in the series is homologous with the tightly bound acyl adenylate intermediate. Adenosine 5'-ethylphosphate (Ki = 33 nM) is 88-fold more potent than adenosine 5'-methylphosphate (Ki = 2900 nM) as a competitive inhibitor of acetyl-CoA synthetase; the contribution of a single carbon to the observed binding energy (-11 kJ/mol) is much larger than is typically observed.