Expanding the Scope of Collision-Induced Dissociation-Cleavable Protein Cross-Linkers
- Author(s): Novitsky, Eric James
- Advisor(s): Rychnovsky, Scott D
- et al.
The dissertation describes the efforts towards synthesizing new collision-induced dissociation-cleavable protein cross-linkers (CID-XLs). Chapter one describes the background of CID-XLs and the various fragmentation pathways molecules undergo during collision-induced dissociation. Chapter two details the design and synthesis of new lysine-reactive, cysteine- reactive, and carboxylic acid-reactive sulfoxide-containing cross-linkers. A mechanism for fragmentation during tandem mass spectroscopy is proposed, and the limits of the sulfoxide functional group prompted investigation into a different CID-XL functional group. Chapter three investigates the trioxane core as a novel cleavable functional group, and two trioxane-containing CID-XLs were synthesized. Chapter four focuses on appending affinity purification to both a sulfoxide-containing and trioxane-containing CID-XL.