Artificial aldolases from peptide dendrimer combinatorial libraries

Abstract

Peptide dendrimers were investigated as synthetic models for aldolase enzymes. Combinatorial libraries were prepared with aldolase active residues such as lysine and proline placed at the dendrimer core or near the surface. On-bead selection for aldolase activity was carried out using the dye-labelled 1,3-diketone 1a, suitable for covalent trapping of enamine-reactive side-chains, and the fluorogenic enolization probe 6. Aldolase dendrimers catalyzed the aldol reaction of acetone, dihydroxyacetone and cyclohexanone with nitrobenzaldehyde. Much like enzymes, the dendrimers exhibited strong aldolase activity in aqueous medium, but were also active in organic solvent. Dendrimer-catalyzed aldol reactions reached complete conversion in 3 h at 25 degrees C with 1 mol% catalyst and gave aldol products with up to 65% ee. A positive dendritic effect in catalysis was observed with both lysine and proline based aldolase dendrimer catalysts.

Glycopeptide dendrimers as Pseudomonas aeruginosa biofilm inhibitors

“…25 Initial studies with enzyme models highlighted multivalency effects of histidine in esterase dendrimers, [26][27][28] and of N-terminal proline in aldolase dendrimers. 29 …”

Pursuing Chemical Efficiency by Using Supported Organocatalysts for Asymmetric Reactions under Aqueous Conditions

“…The library containing free N-termini, Nterminal proline or lysine at the surface, showed to be active in the aldol reaction between cyclohexanone and pnitrobenzaldehyde in an aqueous buffer solution (pH 8.5), affording the corresponding aldol in 54% yield, 33% de and 65% ee. Unfortunately, although these dendritic peptides are active in the reaction between acetone and dihydroxyacetone under aqueous conditions, the aldol products were obtained as racemic mixtures [119].…”

Fluorescence Assays for Biotransformations

“…Enol formation is followed by β -elimination of umbelliferone and the corresponding fl uorescence signal. The probe detects the activity of a variety of small molecule enolization catalysts and is generally useful for screening aldolase type biocatalysts [17] . Alkylation of umbelliferone with allyl bromide, dihydroxylation of the allyl ether double bond, silylation of the primary alcohol, oxidation of the secondary alcohol to the ketone, and acidic deprotection provide excellent yields of the probe.…”