Synthesis and characterization of 1,2-dithiolane modified self-assembling peptides

Document Type

Article

Publication Date

2018

Abstract

This report focuses on the synthesis of an N-terminus 1,2-dithiolane modified self-assembling peptide and the characterization of the resulting self-assembled supramolecular structures. The synthetic route takes advantage of solid-phase peptide synthesis with the on-resin coupling of the dithiolane precursor molecule, 3-(acetylthio)-2-(acetylthiomethyl)propanoic acid, and the microwave-assisted thioacetate deprotection of the peptide N-terminus before final cleavage from the resin to yield the 1,2-dithiolane modified peptide. After the high-performance liquid chromatography (HPLC) purification of the 1,2-dithiolane peptide, derived from the nucleating core of the Aβ peptide associated with Alzheimer's disease, the peptide is shown to self-assemble into cross-β amyloid fibers. Protocols to characterize the amyloid fibers by Fourier-transform infrared spectroscopy (FT-IR), circular dichroism spectroscopy (CD) and transmission electron microscopy (TEM) are presented. The methods of N-terminal modification with a 1,2-dithiolane moiety to well-characterized self-assembling peptides can now be explored as model systems to develop post-assembly modification strategies and explore dynamic covalent chemistry on supramolecular peptide nanofiber surfaces.

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Copyright 2018 JoVE

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Publication Title

Journal of Visualized Experiments

Published Citation

Neves, R., Stephens, K., & Smith-Carpenter, J. E. (2018). Synthesis and Characterization of 1, 2-Dithiolane Modified Self-Assembling Peptides. JoVE (Journal of Visualized Experiments), (138), e58135. https:/doi.org/10.3791/58135

DOI

10.3791/58135

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