Enzymes eliminating stereoisomers

Enzymes can also be used to eliminate an undesired stereoisomer. The enzyme will process only one isomer in a racemic mixture and leave the other stereoisomer untouched. 

The extent and degree of interactions between chiral macromolecules of the body and stereoisomers is a source of observable differences in isomeric drug distribution. Stereoselectivity in drug distribution may occur when tissue or protein binding or uptake is associated with structurally specific receptor, protein, or enzyme binding. Since only unbound or free drug is susceptible to elimination and distribution to receptors and other tissues and fluids, differences in the protein and tissue binding of stereoisomers are reflected in their overall pharmacokinetic profiles. 

Doxacurium is a mixture of three trans, trans-stereoisomers, a dl pair [(1R, 1 R,2S,2 S) and (1S,1 S,2R,2 R)] and a meso form (1R,1 S,2S,2 R). Doxacurium is hydrophilic, has a small volume of distribution, and is distributed primarily to extracellular fluids. It is not metabolized by plasma cholinesterase or hepatic enzymes and does not undergo Hofmann elimination. 

Enzyme-catalyzed eliminations generally proceed by E2 mechanisms and produce only one stereoisomer. Two catalytic groups are involved One abstracts the hydrogen, and the other assists in the departure of the leaving group. The groups are positioned appropriately to allow an anti[Pg.261]

As an example of a molecule with diastereotopic ligands, consider the amino acid L-phenylalanine. The two protons at C-3 are diastereotopic, since substitution of either of them would generate a molecule with two chiral centers. Because the chiral center already present is 5, the two diastereomers would be the 2S,3R and the 25,35 stereoisomers. As in the case of enantiotopic protons, diastereotopic protons are designated pro-R or pro-S. The enzyme phenylalanine ammonia lyase catalyzes the conversion of phenylalanine to trans-cinnamic acid by a process involving anti elimination of the amino group and the 3-pro-S hydrogen. This stereochemical course has been demonstrated using deuterium-labeled L-phenyl-alanine as shown" ... 

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