Selenopeptide self-assembly and oxidation-induced conversion to a thiophenol-ligated product

Abstract

Molecular self-assemblies, particularly amyloid fibrils at the micro- and nanoscale, play a crucial role in understanding biomolecular functions of peptides. Recent efforts show that selenopeptides are being studied to understand the role of selenium (Se) in molecular self-assemblies. In this context, this study reports the synthesis of a Se-containing tripeptide, {Sec(C₆H₅)-Sec(C₆H₅)-Sec(C₆H₅)-NH₂} (1), through solid-phase peptide synthesis (SPPS). Oxidation of 1 with hydrogen peroxide (H₂O₂), followed by in-situ thiophenol (PhSH) ligation, produced the corresponding S-tripeptide, {Cys(C₆H₅)-Cys(C₆H₅)-Cys(C₆H₅)-NH₂} (2). Both tripeptides were characterized using NMR, FT-IR, HR-MS, RP-HPLC, CD spectroscopy, fluorescence spectroscopy and fiber X-ray diffraction. Their molecular self-assemblies were investigated by SEM, TEM, and AFM. Se-tripeptide 1 formed amyloid-like fibrils, which, upon oxidative deselenization and thiol ligation, transformed into flower-like microstructures of S-tripeptide 2. Findings highlight the role of Se in selenopeptide self-assembly and its tunability through chemical modification.

Graphical abstract

A selenium-containing tripeptide was synthesized by SPPS method and transformed into its sulfur analogue through oxidative deselenization followed by in situ thiophenol ligation. This chemical modification induced a transition in self-assembly from amyloid-like fibrils to flower-like microstructures, demonstrating the critical role of selenium in regulating peptide supramolecular architecture.