Our lab focuses on the development of novel applications of mass spectrometry to investigate the chemistry of peptides and proteins both in solution and in the gas phase. We have modified a linear ion trap to accept light emitted from pulsed or continuous wave laser, augmenting the already impressive capabilities of the device with the ability to do photodissociation or spectroscopy based experiments. In addition, we utilize separation chemistry, synthetic chemistry, molecular modeling, and ab initio calculations routinely to complement results obtained by mass spectrometry.

Gas Phase Radical Chemistry:

We have discovered a novel tool for generating radicals site specifically in biological molecules including whole proteins. The resulting chemistry of the peptide or protein is dominated by the radical and can be utilized to direct fragmentation to specific sites under certain conditions. Biomolecule identification can be facilitated in this way by greatly increasing the information content of the data which is extracted from the experiments.

Structure, Folding, and Post-Translational Modifications of Proteins:

Protein structure and folding remain topics of intense interest. Robust methods for the rapid determination of protein structures are lacking. Protein structure is further complicated by the presence of a wide variety of post-translational modifications which are not encoded in the genomic information. This project applies molecular recognition in combination with mass spectrometry to probe the surface structures (including PTMs) of proteins, protein complexes, and larger assemblies. Protein structure can be rapidly probed as a function of various conditions, including the addition of binding ligands, under denaturing conditions, as a function of assembly, etc…

Selected Publications

Sun, Q.; Nelson, H.; Ly, T.; Stoltz, B. M.; Julian, R. R. “Side Chain Chemistry Mediates Backbone Fragmentation in Hydrogen Deficient Peptide Radicals” J. Proteome Res. 2009, 8, 958-966.

Yeh, G. K.; Sun, Q.; Meneses, C.; Julian, R. R. “Rapid Peptide Fragmentation without Electrons, Collisions, Infrared Radiation, or Native Chromophores” J. Am. Soc. Mass Spectrom. 2009, 20, 385-393.

Ly, T: Julian, R. R. “Protein-Metal Interactions of Calmodulin and á Synuclein Monitored by Selective Noncovalent Adduct Protein Probing Mass Spectrometry” J. Am. Soc. Mass Spectrom. 2008, 19, 1663-1672.

Diedrich, J. K., Julian, R. R. “Site Specific Radical Directed Dissociation of Peptides at Phosphorylated Residues” J. Am. Chem. Soc. 2008, 130, 12211-12213.

Ly, T; Pujanauski, B. G.; Sarpong, R.; Julian, R. R. “Surveying Ubiquitin Structure by Noncovalent Attachment of Distance Constrained Bis(crown) Ethers” Anal. Chem. 2008, 80, 5059-5064.

Liu, Z.; Cheng, S.; Gallie, D. R.; Julian, R. R. “Exploring the Mechanism of SNAPP Mass Spectrometry Utilizing Site Directed Mutagenesis to Examine Ubiquitin” Anal. Chem. 2008, 80, 3846-3852.

Spencer, E. A. C.; Ly, T; Julian, R. R. “Formation of the Serine Octamer: Ion Evaporation or Charge Residue?” Int. J. Mass Spectrom. 2008, 270, 166-172.

Ly, T.; Julian, R. R. “Residue Specific Radical Directed Dissociation of Whole Proteins in the Gas Phase” J. Am. Chem. Soc. 2008, 130, 351-358.

Ly, T.; Krout, M.; Pham, D. K.; Tani, K.; Stoltz, B. M.; Julian, R. R. “Synthesis of 2-Quinuclidonium by Eliminating Water: Experimental Quantification of the High Basicity of Extremely Twisted Amides” J. Am. Chem. Soc. 2007, 129, 1864-1865.

Ly, T.; Julian, R. R. “Using ESI-MS to probe protein structure by site-specific noncovalent attachment of 18-crown-6” J. Am. Soc. Mass Spectrom. 2006, 17, 1209-1215.