Peptide–Protein Interactions: From Drug Design to Supramolecular Biomaterials

Abstract

The self-recognition and self-assembly of biomolecules are spontaneous processes that occur in Nature and allow the formation of ordered structures, at the nanoscale or even at the macroscale, under thermodynamic and kinetic equilibrium as a consequence of specific and local interactions. In particular, peptides and peptidomimetics play an elected role, as they may allow a rational approach to elucidate biological mechanisms to develop new drugs, biomaterials, catalysts, or semiconductors. The forces that rule self-recognition and self-assembly processes are weak interactions, such as hydrogen bonding, electrostatic attractions, and van der Waals forces, and they underlie the formation of the secondary structure (e.g., α-helix, β-sheet, polyproline II helix), which plays a key role in all biological processes. Here, we present recent and significant examples whereby design was successfully applied to attain the desired structural motifs toward function. These studies are important to understand the main interactions ruling the biological processes and the onset of many pathologies. The types of secondary structure adopted by peptides during self-assembly have a fundamental importance not only on the type of nano- or macro-structure formed but also on the properties of biomaterials, such as the types of interaction, encapsulation, non-covalent interaction, or covalent interaction, which are ultimately useful for applications in drug delivery.

Development of a Chemically Modified Sensor Based on a Pentapeptide and Its Application for Sensitive Detection of Verbascoside in Extra Virgin Olive Oil

“…Compounds with a higher molecular weight but also with a higher number of hydroxyl groups, such as verbascoside, have a higher number of sites for interaction with peptides [ 76 ]. These interactions can occur via non-covalent bonds, i.e., hydrogen bonds or van der Waals forces [ 77 ] with the formation of complex structures, the assembly process often requiring a combination of multiple interaction sites [ 78 ]. Furthermore, the presence of interactions between the supramolecular structure, i.e., the peptide and the compound of interest, can influence the kinetics of the oxidation-reduction process, increasing the rate of electron transfer to the surface of the modified sensor [ 79 ] and also the result of a synergistic potentiation interaction [ 80 ].…”

Research progress on self-assembled nanodrug delivery systems

“…On the basis of peptide self-assembly, the strategy of ''live selfassembly'' is adopted to enable peptide self-assembly nanomaterials to conduct in situ self-assembly, increase targeting, and release drugs at specific sites, thus pushing nanotechnology into a new stage in biomedical applications. 85,86 The ''living self-assembly'' strategy refers to the small molecules in certain disease exogenous anatomies in living organisms; it stimulates a response to the in situ self-assembly to form an advanced assembly body. 87 EISA is a common approach in policy that can trigger precursor molecular catalysis at specific sites with highly expressed enzymes to form nanostructures through self-assembly.…”

Repair of Peripheral Nerve Injury Using Hydrogels Based on Self-Assembled Peptides

“…During the self-assembly of biomolecule peptides, hydrogen atoms in biomolecules interact with negatively charged particles on the surface of some materials to form hydrogen bonds, which causes the small biomolecules to be arranged in a specific direction in an orderly manner, thus creating a one-dimensional functional nanostructure [35]. At the same time, hydrogen bonding forces, van der Waals forces, and hydrophobic interactions in the peptide α helix play an important role in the overall peptide stability [36].…”