Self-Assembly, Bioactivity, and Nanomaterials Applications of Peptide Conjugates with Bulky Aromatic Terminal Groups

Abstract

The self-assembly and structural and functional properties of peptide conjugates containing bulky terminal aromatic substituents are reviewed with a particular focus on bioactivity. Terminal moieties include Fmoc [fluorenylmethyloxycarbonyl], naphthalene, pyrene, naproxen, diimides of naphthalene or pyrene, and others. These provide a driving force for self-assembly due to π-stacking and hydrophobic interactions, in addition to the hydrogen bonding, electrostatic, and other forces between short peptides. The balance of these interactions leads to a propensity to selfassembly, even for conjugates to single amino acids. The hybrid molecules often form hydrogels built from a network of β-sheet fibrils. The properties of these as biomaterials to support cell culture, or in the development of molecules that can assemble in cells (in response to cellular enzymes, or otherwise) with a range of fascinating bioactivities such as anticancer or antimicrobial activity, are highlighted. In addition, applications of hydrogels as slow-release drug delivery systems and in catalysis and other applications are discussed. The aromatic nature of the substituents also provides a diversity of interesting optoelectronic properties that have been demonstrated in the literature, and an overview of this is also provided. Also discussed are coassembly and enzyme-instructed self-assembly which enable precise tuning and (stimulusresponsive) functionalization of peptide nanostructures.

DNA-templated self-assembly of bradykinin into bioactive nanofibrils

“…The lateral packing and π–π stacking formed by central phenylalanine side chains of adjacent strands also contributes to directionality and further promotes self-assembly along the long axis of DNA duplex. 17,24…”

“…The lateral packing and p-p stacking formed by central phenylalanine side chains of adjacent strands also contributes to directionality and further promotes self-assembly along the long axis of DNA duplex. 17,24 Electron microscopy images of dried BK samples revealed the presence of irregular structures, as shown in Fig. 3B.…”

“…values. This procedure is widely used in the study of peptide self-assembly, 16,17,24,26,33 and by estimating C.A.C. values of BK solutions in the presence or absence of DNA, we can compare the aggregation behavior of the peptide and gain insights into the role of DNA as a mediator of aggregation.…”

“…Nanostructured materials offer significant advantages in the production of therapeutic vehicles as they can act as carriers for active molecules or facilitate a preconcentration effect that enhances the therapeutic potential of bioactive building blocks. [13][14][15][16][17] The utilization of this approach has found particular application in the field of DNA-based therapeutics delivery. In recent years, there has been a growing interest in employing biopolymers as a promising strategy for the development of such architectures.…”

Self-assembled aggregates based on cationic amphiphilic peptides: structural insight

“…20 This latter feature can be modulated by peptide functionalization with polymeric or organic moieties. For instance, derivatization of a peptide with PEG (polyethylene glycol) 21,22 or with glycosyl groups 23 allows increasing its solubility; in contrast, the addition of alkyl chains 24,25 or aromatic moieties [26][27][28] causes a decrease in its solubility. Based on the evidence that peptide aggregation can be opportunely modified, many bioactive peptides have been functionalized and studied.…”