K. Yelekci et Rb. Silverman, EFFECT OF THE LOCUS OF THE OXYGEN-ATOM IN AMINO ETHERS ON THE INACTIVATION OF MONOAMINE-OXIDASE-B, Journal of enzyme inhibition, 13(1), 1998, pp. 31-39
Monoamine oxidase is a flavoenzyme that catalyzes the oxidation of a v
ariety of primary, secondary, and tertiary amines. Although primary al
kylamines, such as heptylamine, and primary arylalkyl amines, such as
phenylethylamine, are excellent substrates for MAO, their analogues ha
ving an electron withdrawing group near the aminomethyl methylene grou
p (1-8) are known to inactivate the enzyme. Inactivation has been attr
ibuted to the inductive effect of the electron-withdrawing group of th
ese analogues. To determine the extent of the proposed inductive effec
t of a heteroatom on MAO B inactivation, a series of oxaheptylamine an
alogues (9-12) were synthesized and tested as inactivators of MAO B. T
he analogues in which the oxygen atom is closest to the alpha-carbon (
9 and 10) inactivate MAO B, but activity slowly returns with time. The
analogues with the oxygen atom farther from the alpha-carbon inactiva
te the enzyme, but activity rapidly returns. These results support the
inductive effect hypothesis for inactivation.