UC San Diego

Over the past three decades considerable efforts have been made to create synthetic versions of enzymes, sometimes called synzymes. Most have failed, and the few so-called successes are at best only marginal exhibiting properties that can barely be described as catalytic. While these synthetic nano-structures look similar to the enzyme active site, they do not have the unique mechanical or dynamic catalytic properties to transform a substrate molecule into the desired product molecule with turnover capability. In our study, a series of synzymes that mimics the active catalytic site of proteases which utilizes serine/hydroxyl, cysteine/sulfhydryl, histidine/imidazole and aspartate/carboxyl groups were designed and fabricated. The acetylation and the deacylation kinetics of the synzyme peptides were studied through molecular modeling and UV/Vis spectrophotometry. The intramolecular interactions of synzyme residues were measured with proton NMR. These synzymes were shown to be able to hydrolyze p- nitrophenyl acetate esters and acetic anhydride. Synzymes with phenylalanines between the cysteine and histidine yield a significantly higher deacylation rate, suggesting that the large bulky R-groups of phenylalanine bends the backbone of the synzyme, thus bringing the cysteine thiol group and the histidine imidazole group closer for acetyl exchange. When oscillating pulse electric field was applied to the synzymes, an increase in acetylation rate is observed, suggesting the possibility that PEF treatment aids the electroconformation change of the synzyme during the catalysis process, which in turn increased its deacylation ability and turnover rate