Self-assembly of amphiphilic peptides into bio-functionalized nanotubes: a novel hydrolase model

Abstract

Herein, we report the construction of a novel hydrolase model via self-assembly of a synthetic amphiphilic short peptide (Fmoc-FFH-CONH 2 ) into nanotubes. The peptide-based self-assembled nanotubes (PepNTs-His) with imidazolyl groups as the catalytic centers exhibit high catalytic activity for p-nitrophenyl acetate (PNPA) hydrolysis. By replacement of the histidine of Fmoc-FFH-CONH 2 with arginine to produce a structurally similar peptide Fmoc-FFR-CONH 2 , guanidyl groups can be presented in the nanotubes through the co-assembly of these two molecules to stabilize the transition state of the hydrolytic reaction. Therefore significantly improved catalytic activity has been achieved by the reasonable distribution of three dominating catalytic factors: catalytic center, binding site and transition state stabilization to the co-assembled peptide nanotubes (PepNTs-His-Arg max ). The resulting hydrolase model shows typical saturation kinetics behaviour to that of natural enzymes and the catalytic efficiency of a single catalytic center is 519-fold higher than that without catalysts. As for a nanotube with multicatalytic centers, a remarkable catalytic efficiency could be achieved with the increase of building blocks. This model suggests that the well ordered and dynamic supramolecular structure is an attractive platform to develop new artificial enzymes to enhance the catalytic activity. Besides, this novel peptidebased material has excellent biocompatibility with human cells and is expected to be applied to organisms as a substitute for natural hydrolases.

Short Peptides in Minimalistic Biocatalyst Design

“…To investigate the role of chemical environment/primary structure in the mechanism of catalytic nanostructures, Fmoc-Phe-Phe-Arg (Figure 5b) was also incorporated into the nanotubes in an effort to provide stable transition state binding sites in the form of guanidyl groups through the method of co-assembly. A co-assembled nanotube structure obtained via this method gave rise to a β-sheet structure which was uninterrupted by the incorporation of Fmoc-Phe-Phe-Arg (confirmed by Circular Dichroism, CD) [29]. The function of these structures can be controlled through co-assembly of two peptides, so that a single catalytic system can integrate various combinations of catalytic and binding sites [25].…”

“…For these molecules, self-assembly is based upon aromatic stacking interactions between the aromatic moieties and the β-sheet-like hydrogen bonding arrangement between the peptides [28]. Liu and co-workers reported functionalised nanotubes based on aromatic peptide amphiphiles as a hydrolase model [29].…”

“…The combination of peptide assembly and inorganic nanoparticles enables another route to produce nanomaterials which may possess catalytic activity as they fulfill the requirements of order, presentation of chemical moieties plus multivalency [27,29,35,43,44]. Nanoparticles decorated with functional ligands are particularly interesting in the development of catalysts based on multivalency.…”

Self-assembled Structures from Amphiphilic Peptides

“…The latter is predominantly occupied by charged and polar amino acids; these are: arginine (R), [6,7] histidine (H), [7,8] lysine (K), [9][10][11][12][13][14][15] aspartic acid (D), [16,17] glutamic acid (E), [11,18] serine (S), threonine (T), asparagine (N), glutamine (Q), and cysteine (C). [13] The design of the hydrophobic part is based on amino acids with neutral and nonpolar side-chains such as glycine (G), [16] alanine (A), [15,19] valine (V), [17,20] leucine (L), [9,17] isoleucine (I), [21] methionine (M), phenylalanine (F), [22,23] tyrosine (Y), and tryptophan (W). [7,[10][11][12][13][14]23] Depending on the hydrophobic to hydrophilic ratio and the sequence, various self-assembled structures can be constructed -as indicated in the associated references for the above amino acids -although the hydrophobicity is moderated by the polar character of the peptide's backbone.…”

Molecular dynamics simulation and conformational analysis of some catalytically active peptides

“…Hence, it would be helpful to find a suitable procedure to design and model easily prepared, stable, and inexpensive artificial enzymes with similar or higher catalytic activities than natural enzymes [1]. The rational design of artificial enzymes is an ongoing area of research that could impact medicine, industrial chemistry, and energy production.…”