Tuning supramolecular chirality in iodinated amphiphilic peptides through tripeptide linker editing Journal Article
| Authors: | MacPherson, D. S.; Dave, D.; Kassem, S.; Doganata, S.; Zeglis, B. M.; Ulijn, R. V. |
| Article Title: | Tuning supramolecular chirality in iodinated amphiphilic peptides through tripeptide linker editing |
| Abstract: | Protease-cleavable supramolecular oligopeptide nanofilaments are promising materials for targeted therapeutics and diagnostics. In these systems, single amino acid substitutions can have profound effects on the supramolecular structure and consequent proteolytic degradation, which are critical parameters for their intended applications. Herein, we describe changes to the self-assembly and proteolytic cleavage of iodine containing sequences for future translation into matrix metalloprotease (MMP-9)-activated supramolecular radio-imaging probes. We use a systematic single amino acid exchange in the tripeptide linker region of these peptide amphiphiles to provide insights into the role of each residue in the supramolecular assemblies. These modifications resulted in dramatic changes in the nature of the assembled structures formed, including an unexpected chiral inversion. By using circular dichroism, atomic force microscopy, Fourier transform infrared spectroscopy, and molecular dynamics simulations, we found that the GD loop, a common motif in β-turn elements, induced a reversal of the chiral orientation of the assembled nanofibers. In addition to the impact on peptide packing and chirality, MMP-9-catalyzed hydrolysis was evaluated for the four peptides, with the β-sheet content found to be a stronger determinant of enzymatic hydrolysis than supramolecular chirality. These observations provide fundamental insights into the sequence design in protease cleavable amphiphilic peptides with the potential for radio-labeling and selective biomedical applications. © 2024 American Chemical Society. |
| Keywords: | controlled study; unclassified drug; amino acid substitution; protein degradation; gelatinase b; molecular dynamics; peptide; amino acid sequence; clinical evaluation; peptides; nuclear magnetic resonance spectroscopy; radiography; amino acid; hydrogen bond; proteinase; catalysis; amino acids; protein secondary structure; oligopeptides; arginylglycylaspartic acid; peptide hydrolases; chemical modification; peptide hydrolase; solvent; iodine; medical applications; circular dichroism; chirality; tri-peptides; matrix metalloproteinase 9; nanomaterial; atomic force microscopy; amphophile; dichroism; iodination; supramolecular chemistry; beta sheet; cellulose; fourier transform infrared spectroscopy; article; proteolytic cleavage; targeted therapeutics; molecular orientation; gene editing; circular dichroism spectroscopy; nanofibers; proteolytic degradation; enzymatic hydrolysis; nanofiber; arginylglycylleucine; arginylprolylleucine; glycylprolylleucine; leucyllysylglycyllysine; tripeptide; amphiphilic peptides; nanofilaments; supramolecular chirality; supramolecular structure |
| Journal Title: | Biomacromolecules |
| Volume: | 25 |
| Issue: | 4 |
| ISSN: | 1525-7797 |
| Publisher: | American Chemical Society |
| Date Published: | 2024-04-08 |
| Start Page: | 2277 |
| End Page: | 2285 |
| Language: | English |
| DOI: | 10.1021/acs.biomac.3c01120 |
| PUBMED: | 38445833 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
