Morphological Versatility in the Self-Assembly of Val-Ala and Ala-Val Dipeptides

Abstract

Since the discovery of dipeptide self-assembly, diphenylalanine (Phe-Phe)-based dipeptides have been widely investigated in a variety of fields. Although various supramolecular Phe-Phe-based structures including tubes, vesicles, fibrils, sheets, necklaces, flakes, ribbons, and wires have been demonstrated by manipulating the external physical or chemical conditions applied, studies of the morphological diversity of dipeptides other than Phe-Phe are still required to understand both how these small molecules respond to external conditions such as the type of solvent and how the peptide sequence affects self-assembly and the corresponding molecular structures. In this work, we investigated the self-assembly of valine-alanine (Val-Ala) and alanine-valine (Ala-Val) dipeptides by varying the solvent medium. It was observed that Val-Ala dipeptide molecules may generate unique self-assembly-based morphologies in response to the solvent medium used. Interestingly, when Ala-Val dipeptides were utilized as a peptide source instead of Val-Ala, we observed distinct differences in the final dipeptide structures. We believe that such manipulation may not only provide us with a better understanding of the fundamentals of the dipeptide self-assembly process but also may enable us to generate novel peptide-based materials for various applications.

Tunable Pentapeptide Self‐Assembled β‐Sheet Hydrogels

“…Oligopeptides that consist of amino acids with aliphatic side chains have received less attention 21, 22. Furthermore, outside of tripeptide assemblies, there have only been a few studies which focused on oligopeptide sequences that are slightly extended in length (4–8 amino acids).…”

“…[21,22] Furthermore,outside of tripeptide assemblies,t here have only been af ew studies which focused on oligopeptide sequences that are slightly extended in length (4-8 amino acids). In af ew cases,t hese studies have been based on short peptide fragments of larger polypeptides already known to self-assemble into nanostructures,s uch as NFGAIL [5,23] (fragment of human islet polypeptide) and KLVFFAE [24] (part of amyloid b [16][17][18][19][20][21][22] ). Most recently,P appas et al utilized ad ynamic combinatorial peptide library with dipeptide inputs and discovered that sequences of four residues (W4, F2L2) and six residues (F6, L6) formed higher-order assemblies.A dditionally,t he eight-residue FDFSFDFS sequence was also able to form aself-supporting hydrogel.…”

Self‐assembly of t‐butyloxycarbonyl protected dipeptide methyl esters composed of leucine, isoleucine, and valine into highly organized structures from alcohol and aqueous alcohol mixtures

“…[31] It was shown that differences in the interactions between peptides and solvent molecules lead to the formation of different peptide structures. The morphology of 2 is similar to Val-Ala obtained from pyridine.…”

“…Nile red stains nanosheets composed of peptoids. [31,40] In the dipeptides where intramolecular hydrogen bonds are unlikely to occur, intermolecular hydrogen bonding and hydrophobic interactions are important determinants of superstructures. Clearly, the surface of the nanotubes composed of aliphatic groups, are hydrophobic enough for a lipophilic dye such as Nile red to bind.…”

“…[38] However, these peptoids are rich in aromatic moieties. [25,31,40] Both TFE and HFIP have lower dielectric constants as compared to MeOH. ThT binds to amyloid fibrils which can be imaged by fluorescence microscopy.…”