A multifunctional surfactant catalyst inspired by hydrolases

Abstract

The remarkable power of enzymes to undertake catalysis frequently stems from their grouping of multiple, complementary chemical units within close proximity around the enzyme active site. Motivated by this, we report here a bioinspired surfactant catalyst that incorporates a variety of chemical functionalities common to hydrolytic enzymes. The textbook hydrolase active site, the catalytic triad, is modeled by positioning the three groups of the triad (-OH, -imidazole, and -CO2H) on a single, trifunctional surfactant molecule. To support this, we recreate the hydrogen bond donating arrangement of the oxyanion hole by imparting surfactant functionality to a guanidinium headgroup. Self-assembly of these amphiphiles in solution drives the collection of functional headgroups into close proximity around a hydrophobic nano-environment, affording hydrolysis of a model ester at rates that challenge α-chymotrypsin. Structural assessment via NMR and XRD, paired with MD simulation and QM calculation, reveals marked similarities of the co-micelle catalyst to native enzymes.

Selective Hydrolysis of Aryl Esters under Acidic and Neutral Conditions by a Synthetic Aspartic Protease Mimic

“…Synthetic esterases are one of the most studied enzyme-mimicking cataysts. , Recent examples, built on peptide or purely abiotic scaffolds, commonly contain either a Lewis acidic metal ion such as zinc to activate water ,− or a catalytic triad to mimic those found in serine proteases. − Although these studies used different reaction conditions, the catalytic efficiency of MINP­( 1 + 5e ) ( k cat / K m = 343 M –1 s –1 at pH 7, 25 °C) compared favorably with those of previously reported systems for PNPA hydrolysis ( k cat / K m = 2–100 M –1 s –1 at pH 6.2–8.0, 22–25 °C), and was close to that (450 M –1 s –1 ) of a synthetic esterase (formed from amyloid fibrils) at pH 8, 38 °C, under high pressure (200 MPa) . The catalytic turnover number (TON) of MINP­( 1 + 5e ) was >510 (Figure b), also significantly higher than those in the literature (mostly >10–20). − …”

Biocatalysts Based on Peptide and Peptide Conjugate Nanostructures

“…It has been shown that catalytic triads from serine proteases (H, S, and D residues) that have been incorporated in a designed lipopeptide-like molecule lead to an effective hydrolase. 197 The peptide surfactant coassembles with conventional cationic surfactants into spherical micelles. Other researchers have explored the use of peptides as agents to bind and template nanoparticles such as gold and silver nanoparticles with a diversity of catalytic properties.…”

“…It has been shown that catalytic triads from serine proteases (H, S, and D residues) that have been incorporated in a designed lipopeptide-like molecule lead to an effective hydrolase . The peptide surfactant coassembles with conventional cationic surfactants into spherical micelles.…”

Systems chemistry of peptide-assemblies for biochemical transformations

“…Further, recent design of minimal peptide based soft nanostructures has been exploited to mimic the advanced function of evolved hydrolytic enzymes. [75][76][77][78][79][80][81][82][83][84][85][86][87][88][89][90][91] In this regard, Stupp and co-workers have designed a peptide amphiphile (histidine groups linked with the N-terminal of KLLLAAA-palmitoyl) with exposed histidine groups that selfassembled to form fibrillar nanostructures which showed excellent hydrolytic activity of the model substrate 2,4-dinitrophenyl acetate. The work highlighted that supramolecular assemblies could expose catalytic residues towards the solvent to feature esterase like activity.…”