Diphenylalanine Motif Drives Self‐Assembling in Hybrid PNA‐Peptide Conjugates

Abstract

Peptides and nucleic acids can self-assemble to give supramolecular structures that find application in different fields, ranging from the delivery of drugs to the obtainment of materials endowed with optical properties. Forces that stabilize the "suprastructures" typically are hydrogen bonds or aromatic interactions; in case of nucleic acids, Watson-Crick pairing drives self-assembly while, in case of peptides, backbone hydrogen bonds and interactions between aromatic side chains trigger the formation of structures, such as nanotubes or ribbons. Molecules containing both aromatic peptides and nucleic acids could in principle exploit different forces to self-assemble. In this work we meant to investigate the self-assembly of mixed systems, with the aim to understand which forces play a major role and determine formation/structure of aggregates. We therefore synthesized conjugates of the peptide FF to the peptide nucleic acid dimer "gc" and characterized their aggregates by different spectroscopic techniques, including NMR, CD and fluorescence.

Chiral Fibers Formation Upon Assembly of Tetraphenylalanine Peptide Conjugated to a PNA Dimer

“…It can be clearly seen that the morphology of the two supramolecular structures is completely different: 4Fat formed visible fibers, whereas the 4Fgc system did not exhibit homogeneous fibers and only small heterogeneous aggregates could be visualized (Figure 5). Morphology of 4Fgc is similar to that observed for FFgc [10] . The 4Fat fibers were arranged in an extended way having a broad distribution of width and length (Figures 5A, C, E and S8): most fibers are 400 nm long and show a width in the range 12–15 nm.…”

“…The PNA heterodimer "gc" conjugated to FF produces mainly spheroids; indeed, samples are not homogeneous, as they contain aggregates of different shape and dimension. [10] Consistent with this observation is the lack of ordered structure in other FF conjugates, containing polyphenylalanine conjugated to the metal chelator DOTA. It was reported that the replacement of FF by 4F resulted in ordered aggregates, in which tetraphenylalanines were arranged in antiparallel beta sheets.…”

“…On the contrary, PNA homodimers conjugated to the peptide FF form fibers in which peptides are arranged in a beta sheet structure. The PNA heterodimer “gc” conjugated to FF produces mainly spheroids; indeed, samples are not homogeneous, as they contain aggregates of different shape and dimension [10] . Consistent with this observation is the lack of ordered structure in other FF conjugates, containing polyphenylalanine conjugated to the metal chelator DOTA.…”

“…In all cases peptides are located at the C-terminal end of the molecules, as previous experiments on FF conjugated to the PNA dimer "gc" at the N or C terminal end showed that aggregation is favored and more ordered structures are obtained when PNA are at the C-terminus. [10] All molecules were synthesized by solid-phase synthesis using standard protocols. [14] The synthetic details and the full chemical characterization are reported in the Supporting Information (Figure S1).…”

Emerging low-molecular weight nucleopeptide-based hydrogels: state of the art, applications, challenges and perspectives

“…29 While not found in Nature (except for the nucleoamino acid willardiine) and that their prebiotic role has been hypothesized, [45][46][47] nucleopeptides are mainly synthetic compounds developed for biological applications 47 thanks to their ability to interact with proteins or enzymes such as serum albumin 48 or the reverse-transcriptase of HIV. 49 Harnessing the abilities of peptides and nucleobases to self-assemble in specific conditions, several research groups reported on the use of nucleopeptides to study their self-organisation and to develop new properties and applications 29 such as tuneable or functional supramolecular architectures, [50][51][52][53] fluorescence, [54][55][56][57] to selectively sequestrate ATP in cells 58 or to deliver RNA into cells, 59 to name a few. In some instances and depending on both the design and the mode of preparation (i.e., the formulation), nucleopeptides are able to form lowmolecular weight gels, an emerging and promising approach to develop innovative soft materials.…”