- Studies on the inhibition of sphingosine-1-phosphate lyase by stabilized reaction intermediates and stereodefined azido phosphates
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Two kinds of inhibitors of the PLP-dependent enzyme sphingosine-1-phosphate lyase have been designed and tested on the bacterial (StS1PL) and the human (hS1PL) enzymes. Amino phosphates 1, 12, and 32, mimicking the intermediate aldimines of the catalytic process, were weak inhibitors on both enzyme sources. On the other hand, a series of stereodefined azido phosphates, resulting from the replacement of the amino group of the natural substrates with an azido group, afforded competitive inhibitors in the low micromolar range on both enzyme sources. This similar behavior represents an experimental evidence of the reported structural similarities for both enzymes at their active site level. Interestingly, the anti-isomers of the non-natural enantiomeric series where the most potent inhibitors on hS1PL.
- Sanllehí, Pol,Abad, José-Luís,Bujons, Jordi,Casas, Josefina,Delgado, Antonio
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supporting information
p. 905 - 915
(2016/08/24)
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- Syntheses of sphingosine-1-phosphate stereoisomers and analogues and their interaction with EDG receptors.
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Sphingosine-1-phosphate (S1P) is considered to be an important regulator of diverse biological processes acting as a natural ligand to EDG receptors. As a preliminary study to develop potent and selective agonist and antagonist for EDG receptors, we report synthesis of S1P stereoisomers and analogues and their binding affinities to EDG-1, -3, and -5.
- Lim, Hyun Suk,Oh, Yong Seok,Suh, Pann Ghill,Chung, Sung Kee
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p. 237 - 240
(2007/10/03)
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