The overall goal of this project is to employ an innovative mass spectrometric technique to detect and characterize modifications to the chirality of individual amino acids within peptides and proteins. Chirality, or the handedness of a molecule, is a crucial attribute that influences both structure and function. Changes in chirality are very difficult to detect;however, a new method dependent on site specific radical migration is extremely sensitive to structure and can detect changes in chirality. The underlying motivation for performing this research is to investigate potential causes of cataract disease and to understand how protein modifications influence aging in general. Changes in chirality have been examined in primarily a generic sense in eye lens proteins previously, and these changes have been noted to increase for cataractous lenses. Site-specific examination of changes in chirality has not been carried out previously because no suitable tool was available for performing the task. The outcome of this project will be detailed information that elucidates how chiral inversion contributes to cataract formation and to aging in general, which is necessary to guide the development of potential preventative treatments.
This research will examine molecular modifications that occur due to aging and are relevant to the formation of cataract, which is the world's leading cause of blindness. A more detailed understanding of these modifications is necessary to guide the development of potential therapies.
|Lyon, Yana A; Beran, Gregory; Julian, Ryan R (2017) Leveraging Electron Transfer Dissociation for Site Selective Radical Generation: Applications for Peptide Epimer Analysis. J Am Soc Mass Spectrom 28:1365-1373|
|R Julian, Ryan (2017) The Mechanism Behind Top-Down UVPD Experiments: Making Sense of Apparent Contradictions. J Am Soc Mass Spectrom 28:1823-1826|
|Lyon, Yana A; Sabbah, Georgette M; Julian, Ryan R (2017) Identification of Sequence Similarities among Isomerization Hotspots in Crystallin Proteins. J Proteome Res 16:1797-1805|
|Lyon, Yana A; Riggs, Dylan; Fornelli, Luca et al. (2017) The Ups and Downs of Repeated Cleavage and Internal Fragment Production in Top-Down Proteomics. J Am Soc Mass Spectrom :|
|Riggs, Dylan L; Gomez, Sonia V; Julian, Ryan R (2017) Sequence and Solution Effects on the Prevalence of d-Isomers Produced by Deamidation. ACS Chem Biol 12:2875-2882|
|Bonner, James; Lyon, Yana A; Nellessen, Christopher et al. (2017) Photoelectron Transfer Dissociation Reveals Surprising Favorability of Zwitterionic States in Large Gaseous Peptides and Proteins. J Am Chem Soc 139:10286-10293|