Self-Assembly Of Amphiphile Peptides And Their Application In Biomimetic Systems

Biomimetics - the science of imitating nature - is a growing multidisciplinaryfield by using the tools of molecular biology,chemistry and nanotechnology, which isnow leading to the fabrication of novel materials with remarkable mechanicalproperties. Through billions of years of evolution nature have produced extremelyefficient materials, which become an increasing source of inspiration for scientists.However, the biological systems are usually extremely complex, so scientists want tomake comparatively simple models to understand their complex mechanism.Furthermore, to mimic the syntheses of these materials, researchers not only emulateparticular biological architecture or system, but importantly to abstract the guidingprinciples and ideas and use such knowledge for the preparation of new syntheticmaterials and devices. Biomimetic mineralization and artificial enzyme are two criticalresearch topics in the field of biomimetic systems.One of most unique and fascinating features of natural biomineralizationprocesses is the controlled growth and hierarchical organization of inorganic mineralsalong with organic materials. Such marvels of nature give excellent physicochemicalproperties to natural biomaterials and provide inspiration for the synthesis of novelfunctional nanomaterials to chemists and materials scientists. For example, naturalbones with excellent mechanical properties are a kind of organic/inorganic hybridmaterials with organic collagen nanofibrils and inorganic calcium phosphatenanocrystals hierarchically organized on a nanoscale. By mimicking natural systems,one may gain insights into biomineralization mechanisms, and synthesize inorganic–organic hybrid materials with potentially interesting functions for applications in nano-and biotechnology. To further expand the scope of application of biomimetic materials,we prepared silver mineralization on self-assembled peptide nanofibers for long termantimicrobial effect.Natural enzymes are large biomacromolecues with extreme molecular complexity, but their mechanism of catalysis is frequently simple with only a few amino acidsinvolved in catalysis. Hence, it is inherently possible to make a comparatively simplemodel of an active site and obtain selective catalysis. Although artificial enzymesconstructed by chemical and genetic strategies previously have demonstrated highcatalytic activity, some disadvantages still remain in such efficient enzyme models. Onthe one hand, catalytic factors are commonly combined into one scaffold throughcovalent chemical methods, which have the limitation of complicated synthetic routes,expensive cost and low productivity. On the other hand, it is difficult to construct theoptimum artificial enzyme via altering the molar ratio of the catalytic factors as it is afixed value. To address this problem,we construct supramolecular models of enzymesbased on peptide with diverse topological structures such as nanofibers, helicalnanofiners and nanotube. These supramolecular models of enzyme based on peptideoffer obvious advantages of ease of fabrication, good biocompatibility, inexpensiveproduction, molecular-recognition capability, and functional flexibility.Among various biological systems, the self-assembly of peptide-based buildingblocks into ordered nanostructures has drawn much attention. Bioactive peptides are atype of suitable building blocks as the objects for fabricating such nanostructuralmaterials because they can be easily synthesized, engineered and modified chemicallyor functionalized biologically. In this research, the diphenylalanine peptide (FF) and itsFmoc-protected derivative were employed as the building blocks which self-assembledinto diverse topological structures such as nanofibers, helical nanofiners and nanotubes.These topological structures were used as scaffolds for application in biomimeticmineralization and artificial enzyme mimic.The research results are as followed:1) We apply peptide nanofibers self-assembled from Fmoc-FFECG as templatesto guide the growth of Ag nanocrystals along with peptide nanofibers. Amphipathicpeptide, Fmoc-FFECG, contain both hydrophobic and hydrophilic moieties. Thehydrophobic group promotes aggregation, which could be used to combineencapsulation of hydrophobic drugs for drug delivery. While the hydrophilic groupdisplay numerous carboxylic acid and thiol groups on peptide nanofiber surface, whichcan serve as nucleation sites for the growth of inorganic materials and metal bindingsites, respectively. In comparison to the traditional Ag-containing materials with silicaor polymer, Ag mineralized peptide nanofibers (Ag–PepNFs) offer obvious advantagesof the ease of fabrication, good biocompatibility, inexpensive production,molecular-recognition capability, and functional flexibility. More importantly, the tubular nanocomposite proves to possess an effective and long-term antibacterialactivity against both Gram-positive and negative bacteria.2) As artificial enzyme mimic. On the one hand, by simulating the catalytic triadstructure of chymotrypsin, we designed and synthesized peptide Fmoc-FFDHS, whichself- assembled to helical nanofibers (Helix-PepNFs) in aqueous solution. The catalytictriad (Asp, His and Ser) were introduced into helical nanofibers and improved enzymeactivity. On the other hand, as the improvement of the system, we apply peptidenanofibers self-assembled from Fmoc- FFH as catalyst center to hydrolase substratePNPA. We further introduced different proportions of guanidine(Fmoc-FFR)into thenanofibers by co-assembly method. In particular, the optimum artificial enzymemodels PepNFs-His-Argmaxwere achieved through changing the molar ratio of catalystcenter and stabilizing the transition state (Fmoc- FFH and Fmoc- FFR). The highactivity of PepNFs-His-Argmaxis attributed to the match degree among the catalyticfactors. This simple preparation process and better match of catalytic factors, theco-assembly nanofibers models may make the preparation of efficient artificial enzymemodels more eassy.3) For the enzyme model of PepNFs-His-Argmax, catalytic centers are combinedinto nanofibers through covalent chemical methods, which have the difficulty toconstruct the optimum artificial enzyme models via altering the molar ratio of thecatalytic factors as it is a fixed value. Thus, as an improvement, we applied peptidenanotubes self-assembled from diphenylalanine peptide (FF) as scaffold toco-assemble with FFH as the catalytic center and FFR as stable transition state bindingsites. In particular, the optimum artificial enzyme models FFNTs-His-Argmaxwereachieved through changing the molar ratio of catalyst center and stabilizing thetransition state (FFH and FFR). Among all the enzyme models we designed in thiswork, FFNTs-His-Argmaxshowed the highest enzyme activity. It is noted that not onlythe specific substrate binding ability but also the better match among the catalyticfactors play an important role in designing a desirable artificial enzyme model.