Jl. Kraus et al., TETRAZOLE ISOSTERES OF BIOLOGICALLY-ACTIVE ACIDS AND THEIR EFFECTS ONENZYMES, Research communications in chemical pathology and pharmacology, 83(2), 1994, pp. 209-222
A number of tetrazole analogs of carboxylic substrates and inhibitors
have been tested. Lactic and pyruvic tetrazoles were found to be compe
titive inhibitors of rabbit muscle L-lactate dehydrogenase in both the
pyruvate reduction and the lactate oxidation reactions (Ki's of 0.04
M and 0.08 M D,L-lactic tetrazole and 0.02 M and 0.035 M pyruvic tetra
zole, respectively). Lactic tetrazole is a non-competitive inhibitor o
f yeast L-lactate dehydrogenase (Ki = 0.10 M D,L-lactic tetrazole) whi
le pyruvic tetrazole is predominantly competitive (Ki = 0.15 M). Alani
ne tetrazole is a poorer substrate than alanine for D-amino acid oxida
se. It also acts as weak inhibitor. Benzoic tetrazole is a substrate-c
ompetitive inhibitor of D-amino acid oxidase (Ki = 0.7 mM) and is also
a stronger ethanol-competitive inhibitor than benzoic acid (Ki = 0.03
M) of liver alcohol dehydrogenase. In all the substrates and inhibito
rs tested, substitution of a tetrazole ring for a carboxylic group has
resulted in decreased binding, presumably due to a dilution of the ne
gative charge density and the larger size of the tetrazoyl anion.