Probing Leucine Side Chain Dynamics in an Amphiphilic Peptide Coprecipitated with Silica using 2H Solid-State NMR

Abstract

There are a number of peptides implicated in the templating of silica morphologies in biological organisms. Biomimetic precipitation studies, aimed at performing the same types of controlled silica precipitation under ambient conditions, have shown that short amphiphilic repeats of leucine and lysine are able to precipitate a variety of interesting nanostructures of silica. Specifically of interest here is LKα14: Ac-LKKLLKLLKKLLKL-C, a synthetic alpha-helical peptide, which has been shown to form a nanospherical coprecipitate with silica. Furthermore, this peptide is known to preaggregate into a tetrameric bundle in solution, with the leucine residues facing inwards to form a hydrophobic core. If this structure persists in silica, the observed morphology could be governed by interactions between the silica and hydrophilic lysine residues. Previous NMR-based structural studies, confirm that the peptide maintains the alpha helical secondary structure in silica, and suggests that the aggregation is maintained. Our goal is to use deuterium solid state nuclear magnetic resonance (2H ssNMR) to establish how the changes in this local environment alter the leucine side chain dynamics of selectively deuterium labeled LKα14. Specifically, we hope to determine if the tetrameric bundle persists, by tracking how the dynamics change going from the neat state, to buffered state, and, finally, to the silica precipitated form. Fitting dynamic models of rotameric and librational motion to the deuterium solid state NMR lineshapes allows us to probe possible mechanisms of peptide pre-aggregation and subsequent silica precipitation.