Polyglutamine diseases are neurodegenerative disorders associated with an expanded chain of glutamines at the N-terminus of the protein which cause the protein to misfold into �-sheets and then aggregate. One common way to study �-sheet formation and aggregation is by using infrared (IR) spectroscopy to probe the strength and alignment of the carbonyls in the protein backbone. However, the vibrations of the glutamine side-chain overlap with those of the protein backbone in the Amide I region of the spectra. Thus, the goal of this work is to separate these IR signals so we can fully interpret the spectra of glutamine-based peptides and proteins. We have synthesized glutamine-based peptides of 4 and 5 residues and analyzed them using IR spectroscopy. Fitting the spectra allows the deconvolution of the side-chain and backbone vibrations and enables us to draw conclusions about the effect of peptide structure and the spacing between glutamine residues on the vibrational frequency of the side chain. We have utilized peptides containing glutamine and alanine residues in various primary sequences to model disordered peptides, varying the spacing of glutamines systematically. Peptides with lysine and glutamic acid at the two termini were used to promote �-sheet formation through electrostatic interactions. Our fits show that both backbone and side chain vibrations are sensitive to secondary structure of the peptide, but that only the side chain vibration depends on the relative position of the two glutamine residues.

Infrared spectra of glutamine-based peptides

247th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.