Metal-Promoted Higher-Order Assembly of Disulfide-Stapled Helical Barrels

• Published in: Nanomaterials (Basel, Switzerland) Vol. 13; no. 19; p. 2645
• Main Authors: Agrahari, Ashutosh, Lipton, Mark, Chmielewski, Jean
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 26.09.2023; MDPI
• Subjects: 3D matrix; Amino acids; amphiphilic peptide; Assembly; Barrels; Biological products; biomaterial; Biomaterials; Biomedical materials; Biotechnology; cargo; Ethylenediaminetetraacetic acid; Growth factors; helical barrel; Hemodialysis; higher order assembly; Hydrophobicity; Ligands; Mass spectrometry; Metal ions; Peptides; Proteins; Scientific imaging; Solvents; United States > US
• ISSN: 2079-4991; 2079-4991
• DOI: 10.3390/nano13192645

Peptide-based helical barrels are a noteworthy building block for hierarchical assembly, with a hydrophobic cavity that can serve as a host for cargo. In this study, disulfide-stapled helical barrels were synthesized containing ligands for metal ions on the hydrophilic face of each amphiphilic peptide helix. The major product of the disulfide-stapling reaction was found to be composed of five amphiphilic peptides, thereby going from a 16-amino-acid peptide to a stapled 80-residue protein in one step. The structure of this pentamer, 5HB1, was optimized in silico, indicating a significant hydrophobic cavity of ~6 Å within a helical barrel. Metal-ion-promoted assembly of the helical barrel building blocks generated higher order assemblies with a three-dimensional (3D) matrix morphology. The matrix was decorated with hydrophobic dyes and His-tagged proteins both before and after assembly, taking advantage of the hydrophobic pocket within the helical barrels and coordination sites within the metal ion-peptide framework. As such, this peptide-based biomaterial has potential for a number of biotechnology applications, including supplying small molecule and protein growth factors during cell and tissue growth within the matrix.