| Small molecule and macromolecule enzyme models for pyridoxamine or pyridoxal-dependent enzymes were studied. It was found that the racemase activity of pyridoxal enzyme models could be selectively increased in preference to transaminase activity by the attachment of rigid basic groups. A tetrahydroquinoline ring was then used to mount the critical functional groups of pyridoxal, and also two examples of rigidly held chirally mounted basic groups. These pyridoxal compounds were able to selectively catalyze decarboxylation, aldol reaction, and retro-aldol reaction of amino acids rather than transamination, and with stereo selectivity.; An enzyme mimic consisting of pyridoxamines covalently linked to polyethyleneimine carrying long-chain alkyl groups were found to be able to convert pyruvic acid to alanine with as much as a 10,000-fold acceleration relative to the reaction with simple pyridoxamine at the same pyridoxamine concentration. The acceleration by polymer was a strong function of the length of the alkyl chains that were appended. It was proposed that the polymer furnished acid and base groups to catalyze the proton transfers that are involved in transamination.; Michaelis-Menten kinetics was seen with many substrates in the polymer catalysis, from which the effect of the lauryl groups and the methyl groups could be determined with respect to the strength of binding of the substrate and the rate constant k2 within the complex. The polyamine catalyzed the reaction using acid and base groups, the lauryl groups increased k2 by producing a nonpolar medium in which the reaction occurs, and the lauryl groups promoted binding of hydrophobic substrates. The result was that the amination of indolepyruvic acid to produce tryptophan was accelerated by 240,000-fold.; PAMAM dendrimers from generations 1--6 were synthesized with pyridoxamine in their core. They transaminated pyruvic and phenylpyruvic acids in water to alanine and phenylalanine, respectively, with Michaelis-Menten kinetics and high effectiveness compared with simple pyridoxamine. The largest dendrimers, similar in size to some globular proteins, were comparable in effectiveness to the polyethylenimine-pyridoxamine catalyst, but not as effective as the polyethylenimine-pyridoxamine carrying lauryl hydrophobic groups. The new catalysts showed both general acid/base catalysis by their amino groups and hydrophobic binding of the phenylpyruvate substrate.; Finally, pyridoxamines carrying hydrophobic sidechains were found to be able to reversibly bind into the hydrophobic core of polyethylenimines, and transaminate ketoacids to amino acids with as much as 725,000-fold rate enhancement. Turnover catalysis was achieved by sacrificial oxidative decarboxylation of C-substituted amino acids, which reconverted the pyridoxals to pyridoxamines. |
