An N-terminal dithioester modified peptide, that is derived from the nucleating core of the Aβ peptide associated with Alzheimer’s disease, was synthetically prepared through solid phase peptide synthesis and purified by high-performance liquid chromatography (HPLC). The resulting cross-β amyloid fiber structures were confirmed by Fourier-transform infrared spectroscopy (FT-IR), matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and transmission electron microscopy (TEM) imaging. The surface reactivity of the supramolecular structure was characterized through a transthioesterification reaction between the dithioester modified peptide in an assembled nanofiber and exogenous thiol containing small molecules. Multiple experiments of varying pH and thiol concentrations were conducted to characterize the thiol-thioester exchange reaction on the amyloid fibers. MALDI mass spectrometry was used to characterize reaction kinetics by following the change in m/z peak intensity ratio of thioester to thiol masses. HPLC analysis was also utilized to validate the data observed with mass spectrometry. The results of these experiments show that the accessible dithioester groups completely react in less than one hour at pH 8 with 50 eq. of the exogenous thiol. These techniques will be used as a model system for the development of post-assembly modifications for a wide variety of potential applications and will allow for further exploration of dynamic disulfide chemistry on the supramolecular peptide fibers.

Exploring dynamic disulfide chemistry on supramolecular fibers

2019 Fall National Meeting

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