The Effect of Adenosine Analogues on the ATP‐Pyrophosphate Exchange Reaction Catalysed by Methionyl‐tRNA Synthetase

Following the finding that the ATP‐PPi exchange reaction and the aminoacylation of tRNA catalysed by methionyl‐tRNA synthetase from Escherichia coli are inhibited by adenosine, numerous analogues of adenosine have been examined to determine the nature of the specificity. The main features observed are as follows. Modifications to positions 1, 2 and 6 of the purine ring of adenosine largely eliminate the inhibition of the ATP‐pyrophosphate exchange reaction. The replacement of the nitrogen at position 7 with a carbon has virtually no effect. Substitutions at positions 8 give analogues exhibiting a wide range of inhibition constants; 8‐aminoadenosine is a highly effective inhibitor, with a K1 300 times lower than that of adenosine. The sugar part of the nucleoside is essential for binding, but can be considerably modified without too great a detrimental effect, particularly in the 5′‐position. For the nucleosides which have a low inhibition constant the presence of a triphosphate group lowers the affinity, but for the analogues exhibiting a high inhibition constant a triphosphate group has no effect.