Search for Fibrous Aggregates Potentially Useful in Regenerative Medicine Formed under Physiological Conditions by Self-Assembling Short Peptides Containing Two Identical Aromatic Amino Acid Residues

Abstract

This study investigates the propensity of short peptides to self-organize and the influence of aggregates on cell cultures. The dipeptides were derived from both enantiomers of identical aromatic amino acids and tripeptides were prepared from two identical aromatic amino acids with one cysteine or methionine residue in the C-terminal, N-terminal, or central position. The formation or absence of fibrous structures under physiological conditions was established using Congo Red and Thioflavine T assays as well as by microscopic examination using normal and polarized light. The in vitro stability of the aggregates in buffered saline solution was assessed over 30 days. Materials with potential for use in regenerative medicine were selected based on the cytotoxicity of the peptides to the endothelial cell line EA.hy 926 and the wettability of the surfaces of the films, as well as using scanning electron microscopy. The criteria were fulfilled by H-dPhedPhe-OH, H-dCysdPhedPhe-OH, H-CysTyrTyr-OH, H-dPhedPhedCys-OH, H-TyrTyrMet-OH, and H–TyrMetTyr–OH. Our preliminary results suggest that the morphology and cell viability of L919 fibroblast cells do not depend on the stereochemistry of the self-organizing peptides.

Non‐Aggregating Amylin Fragments as an Inhibitors of the Aggregation Process of Susceptible to Aggregation Fragments 18–22, 23–27, and 33–37 of Hormone

“…The use of three independent methods has avoided the problem that the fact that methods of studying weak interaction, including self‐organization processes, are associated with a high risk of false results. This approach turned out to be useful in our search for fragments responsible for insulin aggregation as well as in research on the influence of aromatic amino acids on the ability to aggregate short peptides [45–49] . Results of microscopic examination of complexes formed by fragments of amylin (18–22) H‐HSSNN‐OH; (23–27) H‐FGAIL‐OH, (33–37) H‐GSNTY‐NH 2 prone to aggregation with fragments: cyclic (1–7) H‐KCNTATC‐OH, (8–12) H‐ATQRL‐OH, (13–17) H‐ANFLV‐OH, (28–32) H‐SSTNV‐OH devoid of aggregation properties are shown in Figures 3–5.…”

Fibrous Aggregates of Short Peptides Containing Two Distinct Aromatic Amino Acid Residues

“…According to the literature, dipeptides containing two identical aromatic amino acid residues, such as phenylalanine and phenylglycine, tryptophan and histidine, form ordered amyloid‐type spatial structures in a self‐assembly process. We therefore decided to investigate whether this property was due to the presence of two identical aromatic amino acid residues, by testing the ability of a pool of di‐ and tripeptides to self‐organize.…”

“…[26] Moreover, Gazit et al showed that the incorporation of one cysteine residue to the C-terminal position in FF leads to nanospheres instead to typically observed fibers. [27] In our previous study, we investigated the self-assembling properties of several homomeric aromatic dipeptides (containing two identical residues) and of peptides with two identical aromatic residues and cysteine or methionine [28,29] and we also found that incorporation of cysteine residue into peptide chain can change the morphology of aggregates.…”

Recent Progress in Ionic Coassembly of Cationic Peptides and Anionic Species

“…[ 9–12 ] Among the numerous systems, self‐assembled peptide is one of the most important branches, because of its rich chemical diversity, versatile characters, inherent biocompatibility, and bioactivity. [ 13–15 ] Specifically, the natural or chemically engineered amino acids encoded in the sequence of peptide molecules enable the formation of customizable secondary structures, the cooperative interactions between main chains and side chains of peptide molecules can be further leveraged to produce hierarchical nanostructures [ 16–22 ] and important biofunctions, such as drug delivery, [ 23–25 ] tissue engineering, [ 26–28 ] regenerative medicine, [ 29–31 ] and biomineralization. [ 32–35 ] Moreover, many studies have disclosed that self‐assembled peptide nanostructures can offer higher performance (catalytic, therapeutic, targeting, etc.)…”