The modulation of lipase from Candida rugosa activity by peptidomimetics

The library of selected peptidomimetics was synthesised via Passerini 3-component reaction. The SAR study of obtained α-acyloxy carboxamides for the catalytic activity of lipase from Candida rugosa was undertaken. The compounds were tested as potential CRL modulators on model 4-nitrophenol laurate hydrolysis reaction. Subsequently, three activators (EC50: 33-41 nM) and one inhibitor (IC50: 3.35 μM) were identified. The highest activity was observed in the presence of 1-((4-methoxybenzyl)amino)-1-oxo-3-phenylpropan-2-yl 2-phenylacetate, then the CRL was 2.3-fold more active than native enzyme, which was confirmed by kinetic parameters (V_max). The best identified enhancer acts also as an activator of other bacteria lipases, however inhibits enzymes from other species - animal and plant. SAR studies revealed that the amide group has crucial impact on the activity of peptidomimetic. The replacement of substituent at para position in phenyl ring of benzyl amide moiety from methoxy group to hydrogen changes the action of modulator from enhancer to inhibitor. The best activator was also successfully used for enzymatic kinetic resolution of chiral epoxyester shortening the reaction time and increasing more than 10 times the enantioselectivity of this process.