A study of the substrate and inhibitor specificities of AMP aminohydrolase, 5'-nucleotidase, and adenylate kinase with adenosine carboxylates of variable chain length.

A series of AMP analogs in which a terminal carboxylate residue, linked to C 4' of the ribose moiety of adenosine by zero, one, or two methylene groups (1,2,3) or by the unsaturated ethylidene link (4) replaces the phosphate anion, is tested for activity as substrates or effectors of three enzymes known to interact with AMP with a different degree of specificity. 2-4 are substrates of AMP aminohydrolase, 3 and 4 are competitive inhibitors of adenylate kinase, and all acids produce competitive inhibition of the least specific enzyme, 5'-nucleotidase. These activities can be correlated with the intramolecular flexibility of anionic substituent and adenine base which in turn is expressed in typical shifts of the proton magnetic resonance signal of purine H-8. The uronic acid 1, having a rigid molecular conformation, is inactive towards two AMP-dependent enzymes and little active with the third, indicating that this type of compound is not suitable as a nucleotide antagonist whereas nucleoside carboxylates of type 2 and 3 have a higher potential as effectors of nucleotide metabolism.