In this award, funded by the Experimental Physical Chemistry Program of the Chemistry Division, Professor Polavarapu and his students from Vanderbilt University will investigate the molecular structure of Abeta peptides. The conversion of water soluble alpha helical structure into aggregate forming beta sheet structure for full length Abeta peptide [amyloid peptide, Abeta(1-42)] is thought to be responsible for the onset of amyloid disease. To understand this process, the source of initiation of this process needs to be known. Specifically, it is not understood if this structural transition is initiated at a particular amino acid site, or at a certain segment in the Abeta peptide. The purpose of this proposal is to deduce site-specific molecular structural information of Abeta peptide with the use of selected C-13 isotope labels for the amide C=O groups and chiroptical spectroscopy. The main chiroptical spectroscopic method in this project is the newly developed vibrational circular dichroism (VCD) spectroscopy. Accompanying electronic circular dichroism (ECD) spectral studies will also be undertaken in order to supplement the structural information obtained from VCD studies. Vibrational absorption (VA) spectra, which are automatically measured along with VCD spectra, will be used to gain additional structural information. To accomplish the stated goals, isotope labeled short length Abeta peptides will be synthesized and investigated. Simultaneous quantum chemical investigations of vibrational properties will also be undertaken for the isotope labeled short length Abeta peptides to aid in the interpretation of experimental spectra. These combined experimental and quantum chemical investigations on isotope labeled short length peptides are hoped to provide site-specific molecular structural information for Abeta peptide.
Professor Polavarapu will involve students in research and plans outreach activities to a nearby minority serving institution, Tennessee State University. Students from this university will participate in summer research activities, and are invited to attend weekly summer lectures on chiroptical spectroscopy. Also in the summers, week-long workshops on this technique will be held, targeting a mixed audience from chemical industry and academic laboratories.
