|
type |
Journal Article |
authors |
Brinkworth, R. I.; Iles, M. M.; Iskander, M. N.; Andrews, P. R. |
title |
Transition-state analogues as inhibitors of L-dopa decarboxylase |
journal |
Int J Biochem |
Activity |
4.1.1.28 |
ui |
89252411 |
year |
(1988) |
volume |
20 |
number |
11 |
pages |
1273-9 |
| |
keywords |
Animal |
abstract |
1. A series of compounds has been prepared which are analogues of the transition state of the reaction catalysed by L-dopa decarboxylase (EC 4.1.1.28). 2. These compounds are reduced adducts of the substrate (L- dopa) and coenzyme (pyridoxal phosphate), as well as analogues of these substances (D-dopa, pyridoxal and salicaldehyde). 3. Compounds were also prepared with an oxazine link between the 3'-oxygen and the nitrogen attached to the 4'-carbon of the aldehyde moiety. 4. None of the D-dopa adducts produced any significant inhibition, but the L-dopa adducts were all active at millimolar levels, with the oxazine derivatives being more active than their parent compounds. 5. Inhibition was competitive with respect to L-dopa, but was neither competitive nor non-competitive with respect to pyridoxal phosphate. 6. The most active compound tested was the oxazine derivative of the L- dopa/salicaldehyde adduct, with an estimated Ki of 58.0 microM. 7. Increased inhibitory activity was observed when enzyme depleted of pyridoxal phosphate was used. |
last changed |
2002/11/12 16:17 |
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